{"gene":"POSTN","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":1995,"finding":"Recombinant murine OSF-2 (periostin) expressed in baculovirus/insect cells is N-glycosylated (demonstrated by tunicamycin treatment and N-Glycanase digestion causing mobility shifts on Western blot) and binds heparin, suggesting association with bone extracellular matrix after secretion.","method":"Baculovirus expression system, Western blot, tunicamycin treatment, N-Glycanase digestion, endoglycosidase H digestion, heparin-binding assay","journal":"Protein expression and purification","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct biochemical characterization in vitro with multiple methods (glycosylation assays, heparin binding), single study","pmids":["7663166"],"is_preprint":false},{"year":2004,"finding":"Periostin isoforms (including periostin-like-factor/PLF) are expressed during osteoblast differentiation stages; antisense oligonucleotides and blocking antibodies directed against periostin isoforms markedly reduced levels of osteoblast-specific differentiation markers, indicating a functional role in osteoblast differentiation.","method":"Antisense oligonucleotide knockdown, antibody blockade, Western blot, in situ hybridization","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function (antisense + antibody) with defined cellular phenotype (reduced differentiation markers), single lab, two orthogonal methods","pmids":["15258926"],"is_preprint":false},{"year":2004,"finding":"Periostin (chicken ortholog) is expressed in the developing endothelium of ventricular trabeculae, endothelium and mesenchyme of the outflow tract and atrioventricular endocardial cushions, and in valve leaflets and chordae tendinae during fetal development, establishing spatiotemporal localization during cardiac morphogenesis.","method":"Northern analysis, whole mount and section in situ hybridization","journal":"The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by two orthogonal methods (Northern + ISH), single lab, replicated across developmental stages","pmids":["15532025"],"is_preprint":false},{"year":2007,"finding":"BMP-2 signaling through BMPR-1B (ALK6) induces periostin expression at both mRNA and protein levels in atrioventricular cushion mesenchymal cells; conversely, noggin (BMP antagonist) or dominant-negative BMPR-1B represses periostin expression. BMP-2 also induces Twist and Id1 transcripts, which are implicated in periostin promoter activation.","method":"3D collagen gel culture of chick AV cushion mesenchymal cells, constitutively active/dominant-negative viral constructs, qRT-PCR, protein expression analysis","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain- and loss-of-function experiments with viral constructs in primary cells, single lab, two orthogonal methods (mRNA and protein)","pmids":["18261719"],"is_preprint":false},{"year":2009,"finding":"Periostin-like-factor (PLF), a periostin isoform, promotes osteoblast proliferation and differentiation in vitro, and in vivo injection into rat femur bone marrow increases bone formation; PLF expression is robustly upregulated in callus osteoblasts during fracture healing.","method":"Adenoviral overexpression, CyQUANT proliferation assay, alkaline phosphatase staining, von Kossa staining, calcium deposition assay, in vivo intramarrow injection, immunostaining","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function in vitro and in vivo with multiple cellular phenotype readouts, single lab","pmids":["19006175"],"is_preprint":false},{"year":2011,"finding":"Exogenous periostin inhibits ureteral branching morphogenesis and reduces glomerular number in metanephric explant cultures; BMP-4 upregulates periostin mRNA expression in the developing kidney; periostin and its receptor αv integrin are co-expressed in ureteral smooth muscle cells at E15.5.","method":"Metanephric explant culture with recombinant periostin, quantitative RT-PCR, immunofluorescence, RNA in situ hybridization","journal":"The Journal of urology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assay (explant culture with recombinant protein) plus co-localization, single lab, multiple methods","pmids":["21855915"],"is_preprint":false},{"year":2014,"finding":"Periostin deficiency in mice abrogates carbon tetrachloride- and bile duct ligation-induced liver fibrosis; TGF-β1 markedly induces periostin expression in primary hepatic stellate cells; periostin co-localizes with hepatic stellate cell-derived collagen I and α-SMA in fibrotic liver; periostin-null mice show reduced α-SMA, fibronectin, collagen I, and pro-inflammatory cytokine levels after CCl4 treatment.","method":"Periostin-knockout mice, CCl4 and BDL fibrosis models, immunohistochemistry, qRT-PCR, Western blot, primary hepatic stellate cell culture with TGF-β1","journal":"The American journal of pathology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined fibrosis phenotype replicated in two injury models, TGF-β1 induction confirmed in primary cells, multiple orthogonal methods","pmids":["25541330"],"is_preprint":false},{"year":2014,"finding":"Periostin induces expression of IL-6, IL-8, MMP-1, MMP-3, MMP-13, and NOS2 in cultured human chondrocytes in a dose- and time-dependent manner via NF-κB signaling (evidenced by nuclear translocation of p65); NF-κB inactivation suppresses periostin-induced upregulation of these genes.","method":"Primary human chondrocyte culture with recombinant periostin, qRT-PCR, NF-κB inhibition (BAY compound), immunocytochemistry of p65 nuclear translocation","journal":"BMC musculoskeletal disorders","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — recombinant protein treatment with pathway inhibition and defined molecular phenotype, single lab, multiple methods","pmids":["26289167"],"is_preprint":false},{"year":2014,"finding":"Periostin promotes pancreatic β-cell regeneration: injection of periostin into the pancreas stimulated proliferation of vimentin-expressing mesenchymal cells and duct-like cells expressing Ngn3 and Pdx1; Postn-deficient mice show impaired mesenchymal formation and reduced β-cell regeneration after partial pancreatectomy and increased sensitivity to streptozotocin.","method":"Periostin-knockout mice, partial pancreatectomy model, intraperitoneal and intraductal injection of recombinant periostin, immunostaining, glucose tolerance testing","journal":"Endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO plus gain-of-function with recombinant protein, defined cellular phenotype, single lab","pmids":["25485969"],"is_preprint":false},{"year":2014,"finding":"Periostin expression contributes to cortical bone loss during unloading: hindlimb suspension decreases Postn expression and consecutively increases Sost (sclerostin) expression; Postn-null mice do not show increased Sost upon unloading and are protected from cortical bone loss, indicating periostin regulates cortical bone response to mechanical forces through a periostin→sclerostin axis.","method":"Periostin-knockout mice, hindlimb suspension model, bone microstructure analysis, gene expression analysis (Postn, Sost, Dkk1, Rankl, Opg)","journal":"Bone","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with defined mechanical unloading phenotype and mechanistic pathway (Postn→Sost), single lab, multiple readouts","pmids":["25445447"],"is_preprint":false},{"year":2015,"finding":"Mechanical compressive force induces POSTN expression in human periodontal ligament (hPDL) fibroblasts via TGF-β1 signaling: cycloheximide, TGF-β inhibitor (SB431542), or neutralizing antibody against TGF-β1 attenuated force-induced POSTN expression. TGF-β1 accumulated intracellularly/in surrounding matrix (not in medium) upon loading.","method":"Computerized cell compressive force loading apparatus, real-time PCR, Western blot, ELISA, pharmacological inhibition (cycloheximide, SB431542), neutralizing antibody","journal":"Journal of dental research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic pathway (force→TGF-β1→POSTN) tested with multiple inhibitors, single lab","pmids":["25870205"],"is_preprint":false},{"year":2016,"finding":"TAp73 transcription factor directly activates POSTN expression in glioblastoma cells; chromatin immunoprecipitation and reporter assays demonstrate POSTN is a transcriptional target of TAp73; POSTN overexpression rescues the invasive phenotype of glioblastoma cells after p73 knockdown.","method":"siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assay, invasion assay, POSTN overexpression rescue experiment","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and reporter assay directly demonstrate p73 binding to POSTN promoter, rescue experiment confirms functional link, single lab","pmids":["26930720"],"is_preprint":false},{"year":2016,"finding":"POSTN in glioma stem cells (GSCs) regulates invasion and expression of EMT markers (caveolin-1) and angiogenesis-related genes (HIF1α, VEGF-A) through activation of STAT3; recombinant POSTN increases GSC invasion; POSTN expression is associated with acquired resistance to anti-VEGF-A therapy in mouse xenograft models.","method":"Mouse xenograft models, recombinant POSTN treatment, gene expression analysis, STAT3 pathway analysis","journal":"Molecular cancer therapeutics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pathway association in xenograft model with recombinant protein, single lab, limited mechanistic dissection of STAT3 activation","pmids":["27307601"],"is_preprint":false},{"year":2017,"finding":"Periostin's multi-domain structure (EMI domain, four FAS1 domains, C-terminal domain) enables binding to type I collagen, fibronectin, tenascin-C, laminin γ2, BMP-1 (which catalyzes crosslinking of type I collagen), proteoglycans, Notch1, and CCN3; adjacent domains put interacting proteins in close proximity, promoting assembly into extracellular matrix architectures.","method":"Binding domain mapping studies, literature synthesis of domain-protein interaction data","journal":"Journal of cell communication and signaling","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multi-domain binding interactions established across multiple studies, mechanistic rationale for scaffold function supported by converging evidence","pmids":["29086200"],"is_preprint":false},{"year":2017,"finding":"Periostin's multi-domain structure functions as a scaffold for assembly of extracellular matrix proteins; adjacent binding sites on periostin bring interacting proteins (collagen type I and V, fibronectin, tenascin, laminin, CCN3, βig-h3, lysyl oxidase, BMP-1) into close proximity, promoting intermolecular interactions and assembly into extracellular architectures.","method":"Review of direct binding experiments from multiple studies (domain mapping, pulldown assays)","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — protein-protein interactions established by multiple independent binding studies, multi-domain scaffold function supported across labs","pmids":["28887577"],"is_preprint":false},{"year":2017,"finding":"Oligonucleotide-based periostin inhibition (siRNA and antisense oligonucleotide) administered intranasally reduces pulmonary fibrosis in bleomycin-treated mice, decreasing periostin levels, TGF-β1, collagen deposition, and fibrosis scores.","method":"siRNA and antisense oligonucleotide in vivo treatment, bleomycin pulmonary fibrosis model, gene/protein expression analysis, histological fibrosis scoring","journal":"Gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two independent RNA-targeting strategies (siRNA and antisense) with converging results in animal model, single lab","pmids":["28820502"],"is_preprint":false},{"year":2017,"finding":"Periostin blockade using an anti-periostin polyclonal antibody attenuates renal fibrosis in the unilateral ureteral obstruction model by altering TGF-β signaling, inflammatory and apoptotic pathways; integrin blockade peptide decreases fibrosis-related gene expression in vitro; recombinant periostin increases α-SMA expression in collecting duct cells.","method":"Periostin-knockout mice, UUO model, anti-periostin antibody treatment, integrin blockade peptide, recombinant periostin treatment in primary tubular cells, gene expression analysis","journal":"American journal of nephrology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO + antibody blockade + recombinant protein experiments, multiple methods converging on TGF-β/integrin mechanism, single lab","pmids":["29268247"],"is_preprint":false},{"year":2017,"finding":"Aptamer-based blockade of periostin (PA) attenuates TGF-β1-induced upregulation of fibronectin and type I collagen in inner medullary collecting duct cells in vitro, and reduces renal fibrosis in diabetic mice in vivo.","method":"Periostin-binding DNA aptamer treatment, TGF-β1 stimulation of IMCD cells, qRT-PCR, Western blot, immunohistochemistry, Sirius Red staining in diabetic mouse model","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — aptamer-based functional inhibition with parallel in vitro and in vivo validation, single lab, multiple methods","pmids":["28819200"],"is_preprint":false},{"year":2018,"finding":"Genetic deletion of Postn in RIP1-Tag2 mice blunts tumor rebounds of M2-like macrophages and αSMA+ stromal cells after prolonged VEGFA inhibition, suppresses PNET revascularization and progression, and impedes upregulation of FGF2; depleting macrophages with anti-CSF1R antibody similarly inhibits PNET revascularization under VEGFA blockade despite continued POSTN production, placing macrophage recruitment downstream of POSTN.","method":"Genetic Postn deletion in RIP1-Tag2 transgenic mice, VEGFA blockade, anti-CSF1R antibody, tumor histology, gene expression analysis","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO in transgenic tumor model with multiple orthogonal interventions (Postn deletion + macrophage depletion), mechanistic pathway placement established","pmids":["29514082"],"is_preprint":false},{"year":2019,"finding":"Periostin interacts with integrin-β1 to inhibit tubular cell cycle arrest and apoptosis after ischemia-reperfusion injury; periostin-overexpressing mice have more F4/80+ macrophages with increased proliferation and proregenerative factor expression; treating macrophages with recombinant periostin directly induces macrophage proliferation and proregenerative molecule expression.","method":"Conditional tubule-specific periostin overexpression and knockout mice, renal ischemia-reperfusion injury model, primary tubular cell hypoxia-reoxygenation model, macrophage co-culture with recombinant periostin, integrin-β1 interaction studies","journal":"Journal of the American Society of Nephrology : JASN","confidence":"High","confidence_rationale":"Tier 2 / Strong — complementary gain- and loss-of-function mouse models plus in vitro recombinant protein experiments identifying integrin-β1 as the receptor, multiple orthogonal methods, single lab with rigorous controls","pmids":["31690575"],"is_preprint":false},{"year":2019,"finding":"Full-length hPOSTN isoform 1 overexpression in chondrosarcoma cells alters expression of genes with known roles in chondrocyte function and osteoarthritis; cells expressing total POSTN (not isoform 1 specifically) exhibited increased cell adhesion potential, suggesting isoform-specific functional differences.","method":"Stable transfection with pcDNA3.1-hPOSTN-001, RNA-sequencing, cell adhesion assay, siRNA knockdown","journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, overexpression with transcriptomic readout and cell adhesion assay, limited mechanistic depth","pmids":["30991832"],"is_preprint":false},{"year":2019,"finding":"Periostin interacts with tenascin-C (confirmed by co-immunoprecipitation in human microvascular endothelial cells after IL-13 stimulation); single or dual siRNA inhibition of periostin and tenascin-C suppresses angiogenic functions of endothelial cells; periostin-knockout mice show scant tenascin-C expression and attenuated pathological neovascularization in oxygen-induced retinopathy.","method":"Co-immunoprecipitation, siRNA knockdown, in vitro angiogenesis assay, periostin-knockout and tenascin-C-knockout mice, oxygen-induced retinopathy model","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct protein-protein interaction confirmed by Co-IP, functional consequences established by siRNA and genetic KO in two model systems (in vitro and in vivo)","pmids":["32518264"],"is_preprint":false},{"year":2020,"finding":"Periostin interacts with discoidin domain receptor-1 (DDR1), a receptor tyrosine kinase; genetic deficiency or pharmacological inhibition of DDR1 in mouse chondrocytes blocks periostin-induced MMP-13 expression; periostin signals through DDR1 to activate AKT/β-catenin signaling and downstream MMP-13 and ADAMTS4 expression, promoting cartilage collagen and proteoglycan degradation.","method":"DDR1 knockout mouse chondrocytes, DDR1 pharmacological inhibitor, Western blot, gene expression analysis, in vitro cartilage degradation assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO and pharmacological inhibition converge on DDR1 as the periostin receptor for MMP-13 induction, single lab, multiple methods","pmids":["32330138"],"is_preprint":false},{"year":2020,"finding":"CAF-derived POSTN functions as a ligand for integrin αvβ3 on ovarian cancer cells, activating the PI3K/Akt pathway and inducing EMT to enhance cancer cell migration and invasion; TGF-β1-mediated activation of fibroblasts partly relies on POSTN.","method":"Transwell migration/invasion assay, lentiviral POSTN knockdown and overexpression, RNA sequencing, Western blot, indirect co-culture","journal":"Gynecologic oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ligand-receptor interaction (αvβ3) with downstream pathway (PI3K/Akt) and functional cellular phenotype, multiple methods, single lab","pmids":["33317907"],"is_preprint":false},{"year":2020,"finding":"POSTN promotes pulmonary hypertension via a positive feedback loop with HIF-1α: POSTN overexpression activates HIF-1α and increases ET-1 and VEGF production in pulmonary artery endothelial cells; siRNA knockdown of HIF-1α abolishes the proangiogenic effect of POSTN; blockade of TrkB (tyrosine kinase receptor B) attenuates POSTN-induced HIF-1α expression; HIF-1α inhibition reduces POSTN and TrkB expression.","method":"siRNA knockdown of POSTN and HIF-1α in human pulmonary artery endothelial cells, genetic epistasis (Sugen 5416/hypoxia and chronic hypoxia mouse models), TrkB blockade, gene expression analysis","journal":"Circulation research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established by siRNA in cell lines and mouse models, positive feedback loop demonstrated with multiple pathway inhibitors, single lab","pmids":["32752980"],"is_preprint":false},{"year":2020,"finding":"Periostin modulates myofibroblast differentiation and contraction via the integrinβ1/RhoA pathway; periostin is required for formation of focal and fibrillar adhesions in palatal fibroblasts; exogenous recombinant periostin rescues the deficient collagen gel contraction of Postn-/- fibroblasts; Rac inhibition rescues the deficient myofibroblastic phenotype of Postn-/- cells; fibronectin synthesis in response to low stiffness is periostin-dependent.","method":"Periostin-knockout mice, palatal wound model, collagen gel contraction assay, recombinant periostin rescue, silicon substrate stiffness experiments, pharmacological Rac inhibition, immunofluorescence for vinculin and integrinβ1","journal":"Matrix biology : journal of the International Society for Matrix Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with rescue by recombinant protein, defined molecular pathway (integrinβ1/RhoA), stiffness-dependent ECM regulation, multiple orthogonal methods, single rigorous study","pmids":["32777343"],"is_preprint":false},{"year":2020,"finding":"Periostin mediates condylar resorption in TMJ-OA via NF-κB-ADAMTS5 signaling: periostin induces IκBα phosphorylation and degradation, p65 nuclear translocation, and subsequent ADAMTS5 expression in chondrocytes; NF-κB inhibition (BAY 11-7082) rescues periostin-induced ADAMTS5 upregulation.","method":"In vitro pressure chamber model, Western blot (IκBα phosphorylation), immunofluorescence (p65 nuclear translocation), NF-κB inhibitor (BAY 11-7082), gene expression analysis","journal":"Inflammation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined signaling pathway (periostin→NF-κB→ADAMTS5) with pharmacological rescue, single lab, multiple methods","pmids":["31840212"],"is_preprint":false},{"year":2020,"finding":"POSTN promotes vascular calcification in diabetes by blocking autophagic flux in vascular smooth muscle cells: POSTN upregulation impairs autophagosome-lysosome fusion in an intracellular ROS-dependent manner; inhibition of POSTN alleviates AGEs-BSA-induced autophagic flux blockade and attenuates VSMC calcification.","method":"POSTN siRNA knockdown, recombinant POSTN treatment, Western blot (Beclin1, LC3-II, P62), co-localization of LC3-II and LAMP1, ROS measurement, diabetic rat vascular calcification model","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown and recombinant protein with autophagy flux markers and ROS dependence, single lab, multiple methods","pmids":["33744420"],"is_preprint":false},{"year":2020,"finding":"Silencing of POSTN in pericytes in 3D co-culture experiments attenuates vessel number, vessel length, and endothelial junction formation; pericytes are identified as the main source of periostin in human gliomas (co-localization with PDGFRβ+ cells, not OLIG2+/SOX2+ glioma stem cells).","method":"POSTN siRNA silencing, 3D in vitro angiogenesis co-culture model, RT-PCR, immunohistochemistry, double labeling and in situ RNA hybridization","journal":"Journal of neuropathology and experimental neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA loss-of-function in 3D co-culture with defined angiogenesis phenotype, cell type identification by multiple labeling methods, single lab","pmids":["32647861"],"is_preprint":false},{"year":2021,"finding":"POSTN expression in glioblastoma stem cells (GSCs) promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway; ChIP-seq and ChIP-PCR confirmed β-catenin binding to the FOSL1 promoter; POSTN also recruits microglia and upregulates CD70 expression through the αVβ3/PI3K/AKT/NFκB pathway, promoting Treg development and immunosuppression.","method":"POSTN knockdown, tumorsphere formation assay, ChIP-seq and ChIP-PCR, Transwell migration assay, CFSE staining, ELISA, apoptosis assay, patient-derived xenograft model, orthotopic glioma mouse model","journal":"Journal of experimental & clinical cancer research : CR","confidence":"High","confidence_rationale":"Tier 2 / Strong — ChIP-seq/ChIP-PCR directly establishes β-catenin→FOSL1 regulation, multiple functional assays with defined receptor (αVβ3) and bifurcating downstream pathways, in vivo validation, single rigorous study","pmids":["39227950"],"is_preprint":false},{"year":2023,"finding":"Hyperglycemia stimulates periostin expression in cardiac fibroblasts via TGF-β/Smad-dependent signaling; periostin upregulates NAP1L2 expression, which recruits SIRT3 to deacetylate H3K27ac on promoters of BCAA catabolism enzymes (BCAT2 and PP2Cm), resulting in BCAA catabolism impairment; glucosyringic acid specifically targets and inhibits periostin to ameliorate diabetic cardiomyopathy.","method":"RNA sequencing, gain- and loss-of-function experiments (periostin-deficient mice, overexpression), TGF-β/Smad pathway analysis, ChIP for H3K27ac, SIRT3 deacetylation assay, pharmacological targeting (glucosyringic acid), primary cardiomyocyte co-culture","journal":"Cellular & molecular biology letters","confidence":"High","confidence_rationale":"Tier 2 / Strong — RNA-seq guided mechanistic pathway (TGF-β/Smad→POSTN→NAP1L2→SIRT3→BCAA catabolism) with epigenetic mechanistic detail (H3K27ac ChIP), complementary KO and overexpression, pharmacological target validation, multiple orthogonal methods","pmids":["37993768"],"is_preprint":false},{"year":2023,"finding":"Periostin-expressing CAFs (periostin+ CAFs) are spatially enriched at periductal and perivascular/lymphatic vessel margins; genetic depletion of periostin+ CAFs impairs intratumoral collagen organization and inhibits lymphatic (but not lung) metastases; periostin ablation in CAFs reduces their ability to deposit aligned collagen matrices and inhibits cancer cell invasion through collagen and across lymphatic endothelial cell monolayers.","method":"In vivo genetic lineage tracing and ablation of periostin+ cells, collagen organization analysis, Transwell invasion assay across collagen and lymphatic endothelial cell monolayers, in vivo metastasis analysis","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo genetic labeling and ablation with specific phenotypic readouts distinguishing lymphatic vs. lung metastasis, multiple orthogonal in vitro and in vivo methods, mechanistic link to collagen matrix remodeling established","pmids":["37205636"],"is_preprint":false},{"year":2025,"finding":"Periostin marks pulmonary myofibroblasts; ablation of Postn+ myofibroblasts after lung injury ameliorates fibrosis; PIEZO1 is highly expressed in Postn+ myofibroblasts and mediates mechanoactivation; conditional deletion of Piezo1 in Postn+ myofibroblasts suppresses myofibroblast activation and proliferation, disrupts actin organization, and prevents Yap/Taz nuclear localization, shifting myofibroblasts to a stressed/apoptotic state; myofibroblast-specific Yap/Taz deletion recapitulates the protective phenotypes of myofibroblast-Piezo1-KO mice.","method":"Conditional cell-type-specific knockout (Postn-Cre-based Piezo1 and Yap/Taz deletion), cell ablation model, actin organization imaging, Yap/Taz nuclear localization assay, bleomycin-induced fibrosis model","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO of PIEZO1 in Postn+ cells with epistatic Yap/Taz KO confirming the mechanosensing pathway, multiple orthogonal in vivo and cellular phenotype readouts, rigorous genetic approach","pmids":["40454481"],"is_preprint":false}],"current_model":"Periostin (POSTN) is a secreted, N-glycosylated, heparin-binding matricellular protein with a multi-domain structure (EMI domain, four FAS1 domains, C-terminal domain) that functions as an extracellular scaffold by binding collagens (type I/V), fibronectin, tenascin-C, laminin γ2, lysyl oxidase, BMP-1, CCN3, and Notch1, thereby organizing ECM architecture; it signals through cell-surface integrin receptors (αvβ3, αvβ5, α6β4, integrin-β1) and DDR1 to activate PI3K/AKT, NF-κB, Wnt/β-catenin, RhoA/ROCK, FAK, HIF-1α, and STAT3 pathways; its expression is induced by TGF-β1/Smad, BMP-2/BMPR-1B, and IL-4/IL-13 signaling, and by mechanical force via TGF-β1; it is transcriptionally regulated by TAp73 in glioblastoma and HIF-1α under hypoxia; mechanistically, periostin promotes myofibroblast differentiation and collagen fibrillogenesis (via integrinβ1/RhoA), bone formation and osteoblast differentiation, hepatic/renal/pulmonary fibrosis, cartilage degradation (via DDR1→MMP-13/ADAMTS5), pancreatic β-cell regeneration, tumor invasion and lymphatic metastasis (through CAF-mediated collagen remodeling), and in the lung acts as a marker of myofibroblasts whose mechanoactivation requires PIEZO1→Yap/Taz signaling."},"narrative":{"mechanistic_narrative":"Periostin (POSTN) is a secreted, N-glycosylated, heparin-binding matricellular protein whose multi-domain architecture (EMI domain, four FAS1 domains, and a C-terminal domain) lets it act as an extracellular scaffold that brings collagens (type I/V), fibronectin, tenascin-C, laminin, lysyl oxidase, BMP-1, CCN3, and Notch1 into proximity to assemble organized matrix architectures [PMID:29086200, PMID:28887577]. Beyond structural scaffolding, periostin signals as an integrin ligand: it engages integrin-β1, αvβ3, and the receptor tyrosine kinase DDR1 to activate PI3K/AKT/β-catenin, NF-κB, RhoA, and STAT3-type cascades that drive cellular responses to matrix and mechanical cues [PMID:31690575, PMID:32330138, PMID:33317907, PMID:39227950]. A recurring theme is its role in tissue remodeling downstream of TGF-β1/Smad signaling, often induced by mechanical force: periostin is required for myofibroblast differentiation and collagen gel contraction through integrinβ1/RhoA [PMID:32777343], and its deletion protects mice from carbon tetrachloride/bile-duct-ligation liver fibrosis, bleomycin lung fibrosis, and obstructive/diabetic renal fibrosis [PMID:25541330, PMID:28820502, PMID:28819200]. In cartilage it signals via DDR1 to activate AKT/β-catenin and via NF-κB to induce MMP-13 and ADAMTS5, degrading collagen and proteoglycan [PMID:32330138, PMID:31840212]. Periostin also functions in osteoblast and cardiac development, bone responses to mechanical unloading through a periostin→sclerostin axis [PMID:25445447], and supports tumor progression by remodeling collagen in cancer-associated fibroblasts and signaling to cancer and stromal cells to promote invasion, lymphatic metastasis, glioma stem-cell self-renewal, angiogenesis, and immunosuppression [PMID:33317907, PMID:39227950, PMID:37205636]. In injured lung, periostin marks myofibroblasts whose PIEZO1-dependent mechanoactivation drives Yap/Taz-dependent fibrosis [PMID:40454481].","teleology":[{"year":1995,"claim":"Established the basic biochemical nature of the protein, showing periostin is a secreted, N-glycosylated, heparin-binding molecule destined for the bone extracellular matrix.","evidence":"Baculovirus expression with tunicamycin/N-Glycanase glycosylation assays and heparin-binding assay","pmids":["7663166"],"confidence":"Medium","gaps":["No identification of physiological binding partners in vivo","Functional consequence of glycosylation or heparin binding not tested"]},{"year":2004,"claim":"Linked periostin to specific differentiation and developmental programs, showing it is required for osteoblast differentiation and is spatiotemporally expressed during cardiac morphogenesis.","evidence":"Antisense/antibody loss-of-function in osteoblasts and Northern/in situ hybridization in chick heart","pmids":["15258926","15532025"],"confidence":"Medium","gaps":["Molecular mechanism of differentiation control not defined","Receptor and signaling pathway not identified"]},{"year":2007,"claim":"Identified upstream inducers in development, demonstrating BMP-2/BMPR-1B signaling drives periostin expression in cardiac cushion mesenchyme via Twist/Id1.","evidence":"Constitutively-active/dominant-negative viral constructs and noggin in chick AV cushion cells with qRT-PCR","pmids":["18261719"],"confidence":"Medium","gaps":["Direct promoter binding by Twist/Id1 not shown","Downstream periostin function in cushion remodeling not tested here"]},{"year":2009,"claim":"Showed periostin isoform PLF actively promotes bone formation, extending its role from differentiation marker to functional driver of osteoblast proliferation and fracture healing.","evidence":"Adenoviral overexpression in vitro and intramarrow injection in rat femur with mineralization assays","pmids":["19006175"],"confidence":"Medium","gaps":["Receptor/signaling mechanism unresolved","Isoform-specific functions not dissected"]},{"year":2011,"claim":"Demonstrated a regulatory role in kidney organogenesis, with periostin inhibiting branching morphogenesis and co-expressing with its αv integrin receptor.","evidence":"Metanephric explant culture with recombinant periostin, qRT-PCR and immunofluorescence co-localization","pmids":["21855915"],"confidence":"Medium","gaps":["Direct integrin signaling not functionally tested","BMP-4 to periostin promoter link not established"]},{"year":2014,"claim":"Established periostin as a TGF-β1-induced effector of organ fibrosis and a pro-inflammatory/catabolic signaling ligand, central to its remodeling functions.","evidence":"Postn-knockout mice in CCl4/BDL liver fibrosis; recombinant periostin on chondrocytes with NF-κB inhibition; KO/gain-of-function in pancreatic regeneration and bone unloading","pmids":["25541330","26289167","25485969","25445447"],"confidence":"High","gaps":["Surface receptor in fibrosis not pinned to a single integrin","Whether periostin acts on stellate cells autonomously or via collagen scaffolding unclear"]},{"year":2015,"claim":"Defined a mechanotransduction circuit, showing compressive force induces POSTN through locally retained TGF-β1 rather than soluble signaling.","evidence":"Compressive loading of periodontal ligament fibroblasts with TGF-β inhibitor, neutralizing antibody and cycloheximide","pmids":["25870205"],"confidence":"Medium","gaps":["Transcription factors mediating force-induced POSTN not identified","How matrix-retained TGF-β1 is activated by force unresolved"]},{"year":2016,"claim":"Identified transcriptional and signaling regulators in cancer, placing POSTN as a direct TAp73 target and a STAT3-activating driver of glioma invasion and anti-angiogenic resistance.","evidence":"ChIP and luciferase reporter for TAp73; recombinant POSTN and xenograft analyses for STAT3/HIF1α/VEGF","pmids":["26930720","27307601"],"confidence":"Medium","gaps":["Mechanism of STAT3 activation by POSTN not dissected","Receptor mediating glioma effects not defined here"]},{"year":2017,"claim":"Consolidated the scaffold model and validated periostin as a therapeutic target, with its FAS1 domains organizing matrix proteins and RNA/antibody blockade reducing lung and kidney fibrosis.","evidence":"Domain-binding mapping syntheses; intranasal siRNA/antisense in bleomycin lung fibrosis; anti-periostin antibody, aptamer, and integrin-blockade peptide in renal fibrosis models","pmids":["29086200","28887577","28820502","29268247","28819200"],"confidence":"Medium","gaps":["Quantitative stoichiometry of scaffold assembly unknown","Specific integrin engaged in each fibrotic tissue not fully resolved"]},{"year":2018,"claim":"Positioned periostin upstream of tumor stromal remodeling, showing it drives M2 macrophage and αSMA+ stromal rebound and revascularization after anti-VEGFA therapy.","evidence":"Genetic Postn deletion in RIP1-Tag2 mice with VEGFA blockade and anti-CSF1R macrophage depletion","pmids":["29514082"],"confidence":"High","gaps":["Receptor by which POSTN recruits macrophages not identified","Direct vs. matrix-mediated effect on stroma not separated"]},{"year":2019,"claim":"Identified specific receptors and binding partners mediating periostin signaling, establishing integrin-β1 in renal repair/macrophage proliferation and tenascin-C as a direct interactor driving pathological angiogenesis.","evidence":"Conditional tubule Postn gain/loss mice with integrin-β1 interaction studies; Co-IP of periostin with tenascin-C plus siRNA and KO retinopathy models","pmids":["31690575","32518264","30991832"],"confidence":"High","gaps":["Whether integrin-β1 acts directly on macrophages or tubular cells in each context unclear","Isoform-specific functional differences only partly characterized"]},{"year":2020,"claim":"Mapped a network of receptors and downstream pathways across tissues, defining DDR1→AKT/β-catenin for cartilage catabolism, integrinβ1/RhoA for myofibroblast contraction, αvβ3/PI3K/Akt for tumor EMT, and feedback loops in angiogenesis, calcification, and autophagy.","evidence":"DDR1 KO chondrocytes; Postn-KO palatal fibroblasts with recombinant rescue and Rac inhibition; CAF αvβ3 co-culture; HIF-1α/TrkB epistasis; NF-κB-ADAMTS5 and autophagy/ROS assays; pericyte 3D angiogenesis","pmids":["32330138","32777343","33317907","32752980","31840212","33744420","32647861"],"confidence":"High","gaps":["Which receptor predominates when multiple are co-expressed not resolved","How a single ligand selects divergent downstream pathways in different cells unclear"]},{"year":2021,"claim":"Established a complete receptor-to-transcription axis in glioma, showing POSTN drives stem-cell self-renewal via αVβ3/PI3K/AKT/β-catenin/FOSL1 and immunosuppression via NF-κB/CD70.","evidence":"POSTN knockdown, ChIP-seq/ChIP-PCR for β-catenin→FOSL1, tumorsphere and immunosuppression assays, orthotopic and patient-derived xenografts","pmids":["39227950"],"confidence":"High","gaps":["Cellular source of POSTN within the niche not fully assigned","Crosstalk between the two bifurcating pathways not explored"]},{"year":2023,"claim":"Extended periostin into intracellular metabolic and epigenetic regulation, showing TGF-β/Smad-induced periostin impairs cardiac BCAA catabolism through a NAP1L2/SIRT3/H3K27ac axis, and connecting CAF-derived periostin to collagen-alignment-driven lymphatic metastasis.","evidence":"RNA-seq guided KO/overexpression with H3K27ac ChIP and SIRT3 assays in diabetic cardiomyopathy; in vivo lineage tracing and ablation of periostin+ CAFs with collagen/invasion assays","pmids":["37993768","37205636"],"confidence":"High","gaps":["How a secreted matrix protein triggers intracellular NAP1L2 induction is mechanistically incomplete","Generalizability of the lymphatic-specific metastasis effect to other tumors untested"]},{"year":2025,"claim":"Defined the mechanosensing machinery of periostin+ myofibroblasts, placing PIEZO1→Yap/Taz downstream of mechanical activation in lung fibrosis.","evidence":"Postn-Cre conditional Piezo1 and Yap/Taz deletion, cell ablation, actin imaging and bleomycin fibrosis model","pmids":["40454481"],"confidence":"High","gaps":["Whether periostin itself feeds into PIEZO1 activation not tested","Relationship between secreted periostin and intracellular mechanotransduction unresolved"]},{"year":null,"claim":"It remains unclear how a single matricellular ligand selects among its multiple receptors (integrin-β1, αvβ3, DDR1) and divergent downstream pathways in a cell- and context-specific manner, and how secreted periostin connects to its reported intracellular and mechanosensing functions.","evidence":"No single study in the corpus reconciles receptor selection or links extracellular periostin to intracellular signaling","pmids":[],"confidence":"Medium","gaps":["No structural model of receptor selectivity","No unified accounting of extracellular vs. intracellular periostin actions","Isoform-specific receptor preferences undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[19,22,23,29]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[13,14]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[13,14,25]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[13,14,31]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,25]}],"pathway":[{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[13,14,25,31]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[19,22,23,29]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[6,15,17,30]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,3,4,5]}],"complexes":[],"partners":["ITGB1","ITGAV","ITGB3","DDR1","TNC","FN1","BMP1","NOTCH1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15063","full_name":"Periostin","aliases":["Osteoblast-specific factor 2","OSF-2"],"length_aa":836,"mass_kda":93.3,"function":"Induces cell attachment and spreading and plays a role in cell adhesion (PubMed:12235007). 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WASHC4","url":"https://www.omim.org/entry/615748"},{"mim_id":"608777","title":"PERIOSTIN; POSTN","url":"https://www.omim.org/entry/608777"},{"mim_id":"607855","title":"MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT, 1A; MDC1A","url":"https://www.omim.org/entry/607855"},{"mim_id":"603906","title":"CHLORIDE CHANNEL ACCESSORY 1; CLCA1","url":"https://www.omim.org/entry/603906"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"skin 1","ntpm":195.7},{"tissue":"stomach 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POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.","date":"2024","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/38246584","citation_count":38,"is_preprint":false},{"pmid":"28916993","id":"PMC_28916993","title":"Periostin in the pathogenesis of skin diseases.","date":"2017","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/28916993","citation_count":36,"is_preprint":false},{"pmid":"29514082","id":"PMC_29514082","title":"Periostin Limits Tumor Response to VEGFA Inhibition.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29514082","citation_count":36,"is_preprint":false},{"pmid":"17876898","id":"PMC_17876898","title":"Expression of periostin and its clinicopathological relevance in gastric cancer.","date":"2007","source":"World journal of 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domain receptor-1 (DDR1) promotes cartilage degeneration.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32330138","citation_count":29,"is_preprint":false},{"pmid":"32777343","id":"PMC_32777343","title":"Periostin and matrix stiffness combine to regulate myofibroblast differentiation and fibronectin synthesis during palatal healing.","date":"2020","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/32777343","citation_count":29,"is_preprint":false},{"pmid":"32205146","id":"PMC_32205146","title":"Role of serum periostin in the management of asthma and its comorbidities.","date":"2020","source":"Respiratory investigation","url":"https://pubmed.ncbi.nlm.nih.gov/32205146","citation_count":27,"is_preprint":false},{"pmid":"28902360","id":"PMC_28902360","title":"Expression of periostin in breast cancer cells.","date":"2017","source":"International journal of 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Disease.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/36611844","citation_count":25,"is_preprint":false},{"pmid":"32647861","id":"PMC_32647861","title":"Periostin Is Expressed by Pericytes and Is Crucial for Angiogenesis in Glioma.","date":"2020","source":"Journal of neuropathology and experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/32647861","citation_count":25,"is_preprint":false},{"pmid":"31037631","id":"PMC_31037631","title":"The Multiaspect Functions of Periostin in Tumor Progression.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037631","citation_count":25,"is_preprint":false},{"pmid":"28884334","id":"PMC_28884334","title":"Periostin in kidney diseases.","date":"2017","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/28884334","citation_count":24,"is_preprint":false},{"pmid":"31037623","id":"PMC_31037623","title":"Periostin in Bone Biology.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037623","citation_count":24,"is_preprint":false},{"pmid":"37993768","id":"PMC_37993768","title":"Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.","date":"2023","source":"Cellular & molecular biology letters","url":"https://pubmed.ncbi.nlm.nih.gov/37993768","citation_count":24,"is_preprint":false},{"pmid":"32518264","id":"PMC_32518264","title":"Periostin and tenascin-C interaction promotes angiogenesis in ischemic proliferative retinopathy.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32518264","citation_count":24,"is_preprint":false},{"pmid":"31081163","id":"PMC_31081163","title":"Elevation of circular RNA circ-POSTN facilitates cell growth and invasion by sponging miR-1205 in glioma.","date":"2019","source":"Journal of cellular 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pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/31207579","citation_count":22,"is_preprint":false},{"pmid":"31037634","id":"PMC_31037634","title":"Periostin and Integrin Signaling in Stem Cell Regulation.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037634","citation_count":21,"is_preprint":false},{"pmid":"25485969","id":"PMC_25485969","title":"Periostin induces pancreatic regeneration.","date":"2014","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/25485969","citation_count":21,"is_preprint":false},{"pmid":"28819200","id":"PMC_28819200","title":"Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28819200","citation_count":21,"is_preprint":false},{"pmid":"30635868","id":"PMC_30635868","title":"Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.","date":"2019","source":"Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/30635868","citation_count":21,"is_preprint":false},{"pmid":"31840212","id":"PMC_31840212","title":"Periostin Mediates Condylar Resorption via the NF-κB-ADAMTS5 Pathway.","date":"2020","source":"Inflammation","url":"https://pubmed.ncbi.nlm.nih.gov/31840212","citation_count":20,"is_preprint":false},{"pmid":"39227950","id":"PMC_39227950","title":"The dual role of POSTN in maintaining glioblastoma stem cells and the immunosuppressive phenotype of microglia in glioblastoma.","date":"2024","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/39227950","citation_count":19,"is_preprint":false},{"pmid":"37870704","id":"PMC_37870704","title":"The role of periostin in cardiac fibrosis.","date":"2023","source":"Heart failure reviews","url":"https://pubmed.ncbi.nlm.nih.gov/37870704","citation_count":19,"is_preprint":false},{"pmid":"33744420","id":"PMC_33744420","title":"POSTN promotes diabetic vascular calcification by interfering with autophagic flux.","date":"2021","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/33744420","citation_count":19,"is_preprint":false},{"pmid":"31037625","id":"PMC_31037625","title":"Functions of Periostin in Dental Tissues and Its Role in Periodontal Tissue Regeneration.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037625","citation_count":19,"is_preprint":false},{"pmid":"31037633","id":"PMC_31037633","title":"Roles of Periostin in Asthma.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037633","citation_count":18,"is_preprint":false},{"pmid":"35379385","id":"PMC_35379385","title":"Periostin: A Potential Biomarker and Therapeutic Target in Pulmonary Diseases.","date":"2022","source":"Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques","url":"https://pubmed.ncbi.nlm.nih.gov/35379385","citation_count":18,"is_preprint":false},{"pmid":"33280513","id":"PMC_33280513","title":"Role of COL3A1 and POSTN on Pathologic Stages of Esophageal Cancer.","date":"2020","source":"Technology in cancer research & treatment","url":"https://pubmed.ncbi.nlm.nih.gov/33280513","citation_count":18,"is_preprint":false},{"pmid":"31037628","id":"PMC_31037628","title":"Involvement of Periostin in Skin Function and the Pathogenesis of Skin Diseases.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037628","citation_count":18,"is_preprint":false},{"pmid":"35514144","id":"PMC_35514144","title":"Periostin as a biomarker in chronic rhinosinusitis: A contemporary systematic review.","date":"2022","source":"International forum of allergy & rhinology","url":"https://pubmed.ncbi.nlm.nih.gov/35514144","citation_count":18,"is_preprint":false},{"pmid":"31037636","id":"PMC_31037636","title":"Practical Application of Periostin as a Biomarker for Pathological Conditions.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037636","citation_count":17,"is_preprint":false},{"pmid":"38049490","id":"PMC_38049490","title":"Periostin facilitates ovarian cancer recurrence by enhancing cancer stemness.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38049490","citation_count":17,"is_preprint":false},{"pmid":"30935271","id":"PMC_30935271","title":"Periostin and Inflammatory Disease: Implications for Chronic Rhinosinusitis.","date":"2019","source":"Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery","url":"https://pubmed.ncbi.nlm.nih.gov/30935271","citation_count":16,"is_preprint":false},{"pmid":"37205636","id":"PMC_37205636","title":"Periostin+ Stromal Cells Guide Lymphovascular Invasion by Cancer Cells.","date":"2023","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/37205636","citation_count":16,"is_preprint":false},{"pmid":"25592291","id":"PMC_25592291","title":"Loss of periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced Notch1 activity.","date":"2015","source":"Breast cancer research : BCR","url":"https://pubmed.ncbi.nlm.nih.gov/25592291","citation_count":15,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":44478,"output_tokens":9153,"usd":0.135364,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":19427,"output_tokens":5392,"usd":0.115968,"stage2_stop_reason":"end_turn"},"total_usd":0.251332,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1995,\n      \"finding\": \"Recombinant murine OSF-2 (periostin) expressed in baculovirus/insect cells is N-glycosylated (demonstrated by tunicamycin treatment and N-Glycanase digestion causing mobility shifts on Western blot) and binds heparin, suggesting association with bone extracellular matrix after secretion.\",\n      \"method\": \"Baculovirus expression system, Western blot, tunicamycin treatment, N-Glycanase digestion, endoglycosidase H digestion, heparin-binding assay\",\n      \"journal\": \"Protein expression and purification\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct biochemical characterization in vitro with multiple methods (glycosylation assays, heparin binding), single study\",\n      \"pmids\": [\"7663166\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Periostin isoforms (including periostin-like-factor/PLF) are expressed during osteoblast differentiation stages; antisense oligonucleotides and blocking antibodies directed against periostin isoforms markedly reduced levels of osteoblast-specific differentiation markers, indicating a functional role in osteoblast differentiation.\",\n      \"method\": \"Antisense oligonucleotide knockdown, antibody blockade, Western blot, in situ hybridization\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function (antisense + antibody) with defined cellular phenotype (reduced differentiation markers), single lab, two orthogonal methods\",\n      \"pmids\": [\"15258926\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Periostin (chicken ortholog) is expressed in the developing endothelium of ventricular trabeculae, endothelium and mesenchyme of the outflow tract and atrioventricular endocardial cushions, and in valve leaflets and chordae tendinae during fetal development, establishing spatiotemporal localization during cardiac morphogenesis.\",\n      \"method\": \"Northern analysis, whole mount and section in situ hybridization\",\n      \"journal\": \"The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by two orthogonal methods (Northern + ISH), single lab, replicated across developmental stages\",\n      \"pmids\": [\"15532025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"BMP-2 signaling through BMPR-1B (ALK6) induces periostin expression at both mRNA and protein levels in atrioventricular cushion mesenchymal cells; conversely, noggin (BMP antagonist) or dominant-negative BMPR-1B represses periostin expression. BMP-2 also induces Twist and Id1 transcripts, which are implicated in periostin promoter activation.\",\n      \"method\": \"3D collagen gel culture of chick AV cushion mesenchymal cells, constitutively active/dominant-negative viral constructs, qRT-PCR, protein expression analysis\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain- and loss-of-function experiments with viral constructs in primary cells, single lab, two orthogonal methods (mRNA and protein)\",\n      \"pmids\": [\"18261719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Periostin-like-factor (PLF), a periostin isoform, promotes osteoblast proliferation and differentiation in vitro, and in vivo injection into rat femur bone marrow increases bone formation; PLF expression is robustly upregulated in callus osteoblasts during fracture healing.\",\n      \"method\": \"Adenoviral overexpression, CyQUANT proliferation assay, alkaline phosphatase staining, von Kossa staining, calcium deposition assay, in vivo intramarrow injection, immunostaining\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function in vitro and in vivo with multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"19006175\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Exogenous periostin inhibits ureteral branching morphogenesis and reduces glomerular number in metanephric explant cultures; BMP-4 upregulates periostin mRNA expression in the developing kidney; periostin and its receptor αv integrin are co-expressed in ureteral smooth muscle cells at E15.5.\",\n      \"method\": \"Metanephric explant culture with recombinant periostin, quantitative RT-PCR, immunofluorescence, RNA in situ hybridization\",\n      \"journal\": \"The Journal of urology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assay (explant culture with recombinant protein) plus co-localization, single lab, multiple methods\",\n      \"pmids\": [\"21855915\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin deficiency in mice abrogates carbon tetrachloride- and bile duct ligation-induced liver fibrosis; TGF-β1 markedly induces periostin expression in primary hepatic stellate cells; periostin co-localizes with hepatic stellate cell-derived collagen I and α-SMA in fibrotic liver; periostin-null mice show reduced α-SMA, fibronectin, collagen I, and pro-inflammatory cytokine levels after CCl4 treatment.\",\n      \"method\": \"Periostin-knockout mice, CCl4 and BDL fibrosis models, immunohistochemistry, qRT-PCR, Western blot, primary hepatic stellate cell culture with TGF-β1\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined fibrosis phenotype replicated in two injury models, TGF-β1 induction confirmed in primary cells, multiple orthogonal methods\",\n      \"pmids\": [\"25541330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin induces expression of IL-6, IL-8, MMP-1, MMP-3, MMP-13, and NOS2 in cultured human chondrocytes in a dose- and time-dependent manner via NF-κB signaling (evidenced by nuclear translocation of p65); NF-κB inactivation suppresses periostin-induced upregulation of these genes.\",\n      \"method\": \"Primary human chondrocyte culture with recombinant periostin, qRT-PCR, NF-κB inhibition (BAY compound), immunocytochemistry of p65 nuclear translocation\",\n      \"journal\": \"BMC musculoskeletal disorders\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — recombinant protein treatment with pathway inhibition and defined molecular phenotype, single lab, multiple methods\",\n      \"pmids\": [\"26289167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin promotes pancreatic β-cell regeneration: injection of periostin into the pancreas stimulated proliferation of vimentin-expressing mesenchymal cells and duct-like cells expressing Ngn3 and Pdx1; Postn-deficient mice show impaired mesenchymal formation and reduced β-cell regeneration after partial pancreatectomy and increased sensitivity to streptozotocin.\",\n      \"method\": \"Periostin-knockout mice, partial pancreatectomy model, intraperitoneal and intraductal injection of recombinant periostin, immunostaining, glucose tolerance testing\",\n      \"journal\": \"Endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO plus gain-of-function with recombinant protein, defined cellular phenotype, single lab\",\n      \"pmids\": [\"25485969\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin expression contributes to cortical bone loss during unloading: hindlimb suspension decreases Postn expression and consecutively increases Sost (sclerostin) expression; Postn-null mice do not show increased Sost upon unloading and are protected from cortical bone loss, indicating periostin regulates cortical bone response to mechanical forces through a periostin→sclerostin axis.\",\n      \"method\": \"Periostin-knockout mice, hindlimb suspension model, bone microstructure analysis, gene expression analysis (Postn, Sost, Dkk1, Rankl, Opg)\",\n      \"journal\": \"Bone\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with defined mechanical unloading phenotype and mechanistic pathway (Postn→Sost), single lab, multiple readouts\",\n      \"pmids\": [\"25445447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Mechanical compressive force induces POSTN expression in human periodontal ligament (hPDL) fibroblasts via TGF-β1 signaling: cycloheximide, TGF-β inhibitor (SB431542), or neutralizing antibody against TGF-β1 attenuated force-induced POSTN expression. TGF-β1 accumulated intracellularly/in surrounding matrix (not in medium) upon loading.\",\n      \"method\": \"Computerized cell compressive force loading apparatus, real-time PCR, Western blot, ELISA, pharmacological inhibition (cycloheximide, SB431542), neutralizing antibody\",\n      \"journal\": \"Journal of dental research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic pathway (force→TGF-β1→POSTN) tested with multiple inhibitors, single lab\",\n      \"pmids\": [\"25870205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TAp73 transcription factor directly activates POSTN expression in glioblastoma cells; chromatin immunoprecipitation and reporter assays demonstrate POSTN is a transcriptional target of TAp73; POSTN overexpression rescues the invasive phenotype of glioblastoma cells after p73 knockdown.\",\n      \"method\": \"siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assay, invasion assay, POSTN overexpression rescue experiment\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and reporter assay directly demonstrate p73 binding to POSTN promoter, rescue experiment confirms functional link, single lab\",\n      \"pmids\": [\"26930720\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"POSTN in glioma stem cells (GSCs) regulates invasion and expression of EMT markers (caveolin-1) and angiogenesis-related genes (HIF1α, VEGF-A) through activation of STAT3; recombinant POSTN increases GSC invasion; POSTN expression is associated with acquired resistance to anti-VEGF-A therapy in mouse xenograft models.\",\n      \"method\": \"Mouse xenograft models, recombinant POSTN treatment, gene expression analysis, STAT3 pathway analysis\",\n      \"journal\": \"Molecular cancer therapeutics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pathway association in xenograft model with recombinant protein, single lab, limited mechanistic dissection of STAT3 activation\",\n      \"pmids\": [\"27307601\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Periostin's multi-domain structure (EMI domain, four FAS1 domains, C-terminal domain) enables binding to type I collagen, fibronectin, tenascin-C, laminin γ2, BMP-1 (which catalyzes crosslinking of type I collagen), proteoglycans, Notch1, and CCN3; adjacent domains put interacting proteins in close proximity, promoting assembly into extracellular matrix architectures.\",\n      \"method\": \"Binding domain mapping studies, literature synthesis of domain-protein interaction data\",\n      \"journal\": \"Journal of cell communication and signaling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multi-domain binding interactions established across multiple studies, mechanistic rationale for scaffold function supported by converging evidence\",\n      \"pmids\": [\"29086200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Periostin's multi-domain structure functions as a scaffold for assembly of extracellular matrix proteins; adjacent binding sites on periostin bring interacting proteins (collagen type I and V, fibronectin, tenascin, laminin, CCN3, βig-h3, lysyl oxidase, BMP-1) into close proximity, promoting intermolecular interactions and assembly into extracellular architectures.\",\n      \"method\": \"Review of direct binding experiments from multiple studies (domain mapping, pulldown assays)\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — protein-protein interactions established by multiple independent binding studies, multi-domain scaffold function supported across labs\",\n      \"pmids\": [\"28887577\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Oligonucleotide-based periostin inhibition (siRNA and antisense oligonucleotide) administered intranasally reduces pulmonary fibrosis in bleomycin-treated mice, decreasing periostin levels, TGF-β1, collagen deposition, and fibrosis scores.\",\n      \"method\": \"siRNA and antisense oligonucleotide in vivo treatment, bleomycin pulmonary fibrosis model, gene/protein expression analysis, histological fibrosis scoring\",\n      \"journal\": \"Gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two independent RNA-targeting strategies (siRNA and antisense) with converging results in animal model, single lab\",\n      \"pmids\": [\"28820502\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Periostin blockade using an anti-periostin polyclonal antibody attenuates renal fibrosis in the unilateral ureteral obstruction model by altering TGF-β signaling, inflammatory and apoptotic pathways; integrin blockade peptide decreases fibrosis-related gene expression in vitro; recombinant periostin increases α-SMA expression in collecting duct cells.\",\n      \"method\": \"Periostin-knockout mice, UUO model, anti-periostin antibody treatment, integrin blockade peptide, recombinant periostin treatment in primary tubular cells, gene expression analysis\",\n      \"journal\": \"American journal of nephrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO + antibody blockade + recombinant protein experiments, multiple methods converging on TGF-β/integrin mechanism, single lab\",\n      \"pmids\": [\"29268247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Aptamer-based blockade of periostin (PA) attenuates TGF-β1-induced upregulation of fibronectin and type I collagen in inner medullary collecting duct cells in vitro, and reduces renal fibrosis in diabetic mice in vivo.\",\n      \"method\": \"Periostin-binding DNA aptamer treatment, TGF-β1 stimulation of IMCD cells, qRT-PCR, Western blot, immunohistochemistry, Sirius Red staining in diabetic mouse model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — aptamer-based functional inhibition with parallel in vitro and in vivo validation, single lab, multiple methods\",\n      \"pmids\": [\"28819200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Genetic deletion of Postn in RIP1-Tag2 mice blunts tumor rebounds of M2-like macrophages and αSMA+ stromal cells after prolonged VEGFA inhibition, suppresses PNET revascularization and progression, and impedes upregulation of FGF2; depleting macrophages with anti-CSF1R antibody similarly inhibits PNET revascularization under VEGFA blockade despite continued POSTN production, placing macrophage recruitment downstream of POSTN.\",\n      \"method\": \"Genetic Postn deletion in RIP1-Tag2 transgenic mice, VEGFA blockade, anti-CSF1R antibody, tumor histology, gene expression analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO in transgenic tumor model with multiple orthogonal interventions (Postn deletion + macrophage depletion), mechanistic pathway placement established\",\n      \"pmids\": [\"29514082\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Periostin interacts with integrin-β1 to inhibit tubular cell cycle arrest and apoptosis after ischemia-reperfusion injury; periostin-overexpressing mice have more F4/80+ macrophages with increased proliferation and proregenerative factor expression; treating macrophages with recombinant periostin directly induces macrophage proliferation and proregenerative molecule expression.\",\n      \"method\": \"Conditional tubule-specific periostin overexpression and knockout mice, renal ischemia-reperfusion injury model, primary tubular cell hypoxia-reoxygenation model, macrophage co-culture with recombinant periostin, integrin-β1 interaction studies\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — complementary gain- and loss-of-function mouse models plus in vitro recombinant protein experiments identifying integrin-β1 as the receptor, multiple orthogonal methods, single lab with rigorous controls\",\n      \"pmids\": [\"31690575\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Full-length hPOSTN isoform 1 overexpression in chondrosarcoma cells alters expression of genes with known roles in chondrocyte function and osteoarthritis; cells expressing total POSTN (not isoform 1 specifically) exhibited increased cell adhesion potential, suggesting isoform-specific functional differences.\",\n      \"method\": \"Stable transfection with pcDNA3.1-hPOSTN-001, RNA-sequencing, cell adhesion assay, siRNA knockdown\",\n      \"journal\": \"FASEB journal : official publication of the Federation of American Societies for Experimental Biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, overexpression with transcriptomic readout and cell adhesion assay, limited mechanistic depth\",\n      \"pmids\": [\"30991832\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Periostin interacts with tenascin-C (confirmed by co-immunoprecipitation in human microvascular endothelial cells after IL-13 stimulation); single or dual siRNA inhibition of periostin and tenascin-C suppresses angiogenic functions of endothelial cells; periostin-knockout mice show scant tenascin-C expression and attenuated pathological neovascularization in oxygen-induced retinopathy.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, in vitro angiogenesis assay, periostin-knockout and tenascin-C-knockout mice, oxygen-induced retinopathy model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct protein-protein interaction confirmed by Co-IP, functional consequences established by siRNA and genetic KO in two model systems (in vitro and in vivo)\",\n      \"pmids\": [\"32518264\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin interacts with discoidin domain receptor-1 (DDR1), a receptor tyrosine kinase; genetic deficiency or pharmacological inhibition of DDR1 in mouse chondrocytes blocks periostin-induced MMP-13 expression; periostin signals through DDR1 to activate AKT/β-catenin signaling and downstream MMP-13 and ADAMTS4 expression, promoting cartilage collagen and proteoglycan degradation.\",\n      \"method\": \"DDR1 knockout mouse chondrocytes, DDR1 pharmacological inhibitor, Western blot, gene expression analysis, in vitro cartilage degradation assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO and pharmacological inhibition converge on DDR1 as the periostin receptor for MMP-13 induction, single lab, multiple methods\",\n      \"pmids\": [\"32330138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CAF-derived POSTN functions as a ligand for integrin αvβ3 on ovarian cancer cells, activating the PI3K/Akt pathway and inducing EMT to enhance cancer cell migration and invasion; TGF-β1-mediated activation of fibroblasts partly relies on POSTN.\",\n      \"method\": \"Transwell migration/invasion assay, lentiviral POSTN knockdown and overexpression, RNA sequencing, Western blot, indirect co-culture\",\n      \"journal\": \"Gynecologic oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ligand-receptor interaction (αvβ3) with downstream pathway (PI3K/Akt) and functional cellular phenotype, multiple methods, single lab\",\n      \"pmids\": [\"33317907\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"POSTN promotes pulmonary hypertension via a positive feedback loop with HIF-1α: POSTN overexpression activates HIF-1α and increases ET-1 and VEGF production in pulmonary artery endothelial cells; siRNA knockdown of HIF-1α abolishes the proangiogenic effect of POSTN; blockade of TrkB (tyrosine kinase receptor B) attenuates POSTN-induced HIF-1α expression; HIF-1α inhibition reduces POSTN and TrkB expression.\",\n      \"method\": \"siRNA knockdown of POSTN and HIF-1α in human pulmonary artery endothelial cells, genetic epistasis (Sugen 5416/hypoxia and chronic hypoxia mouse models), TrkB blockade, gene expression analysis\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established by siRNA in cell lines and mouse models, positive feedback loop demonstrated with multiple pathway inhibitors, single lab\",\n      \"pmids\": [\"32752980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin modulates myofibroblast differentiation and contraction via the integrinβ1/RhoA pathway; periostin is required for formation of focal and fibrillar adhesions in palatal fibroblasts; exogenous recombinant periostin rescues the deficient collagen gel contraction of Postn-/- fibroblasts; Rac inhibition rescues the deficient myofibroblastic phenotype of Postn-/- cells; fibronectin synthesis in response to low stiffness is periostin-dependent.\",\n      \"method\": \"Periostin-knockout mice, palatal wound model, collagen gel contraction assay, recombinant periostin rescue, silicon substrate stiffness experiments, pharmacological Rac inhibition, immunofluorescence for vinculin and integrinβ1\",\n      \"journal\": \"Matrix biology : journal of the International Society for Matrix Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with rescue by recombinant protein, defined molecular pathway (integrinβ1/RhoA), stiffness-dependent ECM regulation, multiple orthogonal methods, single rigorous study\",\n      \"pmids\": [\"32777343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin mediates condylar resorption in TMJ-OA via NF-κB-ADAMTS5 signaling: periostin induces IκBα phosphorylation and degradation, p65 nuclear translocation, and subsequent ADAMTS5 expression in chondrocytes; NF-κB inhibition (BAY 11-7082) rescues periostin-induced ADAMTS5 upregulation.\",\n      \"method\": \"In vitro pressure chamber model, Western blot (IκBα phosphorylation), immunofluorescence (p65 nuclear translocation), NF-κB inhibitor (BAY 11-7082), gene expression analysis\",\n      \"journal\": \"Inflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined signaling pathway (periostin→NF-κB→ADAMTS5) with pharmacological rescue, single lab, multiple methods\",\n      \"pmids\": [\"31840212\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"POSTN promotes vascular calcification in diabetes by blocking autophagic flux in vascular smooth muscle cells: POSTN upregulation impairs autophagosome-lysosome fusion in an intracellular ROS-dependent manner; inhibition of POSTN alleviates AGEs-BSA-induced autophagic flux blockade and attenuates VSMC calcification.\",\n      \"method\": \"POSTN siRNA knockdown, recombinant POSTN treatment, Western blot (Beclin1, LC3-II, P62), co-localization of LC3-II and LAMP1, ROS measurement, diabetic rat vascular calcification model\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown and recombinant protein with autophagy flux markers and ROS dependence, single lab, multiple methods\",\n      \"pmids\": [\"33744420\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Silencing of POSTN in pericytes in 3D co-culture experiments attenuates vessel number, vessel length, and endothelial junction formation; pericytes are identified as the main source of periostin in human gliomas (co-localization with PDGFRβ+ cells, not OLIG2+/SOX2+ glioma stem cells).\",\n      \"method\": \"POSTN siRNA silencing, 3D in vitro angiogenesis co-culture model, RT-PCR, immunohistochemistry, double labeling and in situ RNA hybridization\",\n      \"journal\": \"Journal of neuropathology and experimental neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA loss-of-function in 3D co-culture with defined angiogenesis phenotype, cell type identification by multiple labeling methods, single lab\",\n      \"pmids\": [\"32647861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"POSTN expression in glioblastoma stem cells (GSCs) promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway; ChIP-seq and ChIP-PCR confirmed β-catenin binding to the FOSL1 promoter; POSTN also recruits microglia and upregulates CD70 expression through the αVβ3/PI3K/AKT/NFκB pathway, promoting Treg development and immunosuppression.\",\n      \"method\": \"POSTN knockdown, tumorsphere formation assay, ChIP-seq and ChIP-PCR, Transwell migration assay, CFSE staining, ELISA, apoptosis assay, patient-derived xenograft model, orthotopic glioma mouse model\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ChIP-seq/ChIP-PCR directly establishes β-catenin→FOSL1 regulation, multiple functional assays with defined receptor (αVβ3) and bifurcating downstream pathways, in vivo validation, single rigorous study\",\n      \"pmids\": [\"39227950\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Hyperglycemia stimulates periostin expression in cardiac fibroblasts via TGF-β/Smad-dependent signaling; periostin upregulates NAP1L2 expression, which recruits SIRT3 to deacetylate H3K27ac on promoters of BCAA catabolism enzymes (BCAT2 and PP2Cm), resulting in BCAA catabolism impairment; glucosyringic acid specifically targets and inhibits periostin to ameliorate diabetic cardiomyopathy.\",\n      \"method\": \"RNA sequencing, gain- and loss-of-function experiments (periostin-deficient mice, overexpression), TGF-β/Smad pathway analysis, ChIP for H3K27ac, SIRT3 deacetylation assay, pharmacological targeting (glucosyringic acid), primary cardiomyocyte co-culture\",\n      \"journal\": \"Cellular & molecular biology letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RNA-seq guided mechanistic pathway (TGF-β/Smad→POSTN→NAP1L2→SIRT3→BCAA catabolism) with epigenetic mechanistic detail (H3K27ac ChIP), complementary KO and overexpression, pharmacological target validation, multiple orthogonal methods\",\n      \"pmids\": [\"37993768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Periostin-expressing CAFs (periostin+ CAFs) are spatially enriched at periductal and perivascular/lymphatic vessel margins; genetic depletion of periostin+ CAFs impairs intratumoral collagen organization and inhibits lymphatic (but not lung) metastases; periostin ablation in CAFs reduces their ability to deposit aligned collagen matrices and inhibits cancer cell invasion through collagen and across lymphatic endothelial cell monolayers.\",\n      \"method\": \"In vivo genetic lineage tracing and ablation of periostin+ cells, collagen organization analysis, Transwell invasion assay across collagen and lymphatic endothelial cell monolayers, in vivo metastasis analysis\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo genetic labeling and ablation with specific phenotypic readouts distinguishing lymphatic vs. lung metastasis, multiple orthogonal in vitro and in vivo methods, mechanistic link to collagen matrix remodeling established\",\n      \"pmids\": [\"37205636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Periostin marks pulmonary myofibroblasts; ablation of Postn+ myofibroblasts after lung injury ameliorates fibrosis; PIEZO1 is highly expressed in Postn+ myofibroblasts and mediates mechanoactivation; conditional deletion of Piezo1 in Postn+ myofibroblasts suppresses myofibroblast activation and proliferation, disrupts actin organization, and prevents Yap/Taz nuclear localization, shifting myofibroblasts to a stressed/apoptotic state; myofibroblast-specific Yap/Taz deletion recapitulates the protective phenotypes of myofibroblast-Piezo1-KO mice.\",\n      \"method\": \"Conditional cell-type-specific knockout (Postn-Cre-based Piezo1 and Yap/Taz deletion), cell ablation model, actin organization imaging, Yap/Taz nuclear localization assay, bleomycin-induced fibrosis model\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO of PIEZO1 in Postn+ cells with epistatic Yap/Taz KO confirming the mechanosensing pathway, multiple orthogonal in vivo and cellular phenotype readouts, rigorous genetic approach\",\n      \"pmids\": [\"40454481\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Periostin (POSTN) is a secreted, N-glycosylated, heparin-binding matricellular protein with a multi-domain structure (EMI domain, four FAS1 domains, C-terminal domain) that functions as an extracellular scaffold by binding collagens (type I/V), fibronectin, tenascin-C, laminin γ2, lysyl oxidase, BMP-1, CCN3, and Notch1, thereby organizing ECM architecture; it signals through cell-surface integrin receptors (αvβ3, αvβ5, α6β4, integrin-β1) and DDR1 to activate PI3K/AKT, NF-κB, Wnt/β-catenin, RhoA/ROCK, FAK, HIF-1α, and STAT3 pathways; its expression is induced by TGF-β1/Smad, BMP-2/BMPR-1B, and IL-4/IL-13 signaling, and by mechanical force via TGF-β1; it is transcriptionally regulated by TAp73 in glioblastoma and HIF-1α under hypoxia; mechanistically, periostin promotes myofibroblast differentiation and collagen fibrillogenesis (via integrinβ1/RhoA), bone formation and osteoblast differentiation, hepatic/renal/pulmonary fibrosis, cartilage degradation (via DDR1→MMP-13/ADAMTS5), pancreatic β-cell regeneration, tumor invasion and lymphatic metastasis (through CAF-mediated collagen remodeling), and in the lung acts as a marker of myofibroblasts whose mechanoactivation requires PIEZO1→Yap/Taz signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Periostin (POSTN) is a secreted, N-glycosylated, heparin-binding matricellular protein whose multi-domain architecture (EMI domain, four FAS1 domains, and a C-terminal domain) lets it act as an extracellular scaffold that brings collagens (type I/V), fibronectin, tenascin-C, laminin, lysyl oxidase, BMP-1, CCN3, and Notch1 into proximity to assemble organized matrix architectures [#13, #14]. Beyond structural scaffolding, periostin signals as an integrin ligand: it engages integrin-\\u03b21, \\u03b1v\\u03b23, and the receptor tyrosine kinase DDR1 to activate PI3K/AKT/\\u03b2-catenin, NF-\\u03baB, RhoA, and STAT3-type cascades that drive cellular responses to matrix and mechanical cues [#19, #22, #23, #29]. A recurring theme is its role in tissue remodeling downstream of TGF-\\u03b21/Smad signaling, often induced by mechanical force: periostin is required for myofibroblast differentiation and collagen gel contraction through integrin\\u03b21/RhoA [#25], and its deletion protects mice from carbon tetrachloride/bile-duct-ligation liver fibrosis, bleomycin lung fibrosis, and obstructive/diabetic renal fibrosis [#6, #15, #17]. In cartilage it signals via DDR1 to activate AKT/\\u03b2-catenin and via NF-\\u03baB to induce MMP-13 and ADAMTS5, degrading collagen and proteoglycan [#22, #26]. Periostin also functions in osteoblast and cardiac development, bone responses to mechanical unloading through a periostin\\u2192sclerostin axis [#9], and supports tumor progression by remodeling collagen in cancer-associated fibroblasts and signaling to cancer and stromal cells to promote invasion, lymphatic metastasis, glioma stem-cell self-renewal, angiogenesis, and immunosuppression [#23, #29, #31]. In injured lung, periostin marks myofibroblasts whose PIEZO1-dependent mechanoactivation drives Yap/Taz-dependent fibrosis [#32].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Established the basic biochemical nature of the protein, showing periostin is a secreted, N-glycosylated, heparin-binding molecule destined for the bone extracellular matrix.\",\n      \"evidence\": \"Baculovirus expression with tunicamycin/N-Glycanase glycosylation assays and heparin-binding assay\",\n      \"pmids\": [\"7663166\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No identification of physiological binding partners in vivo\", \"Functional consequence of glycosylation or heparin binding not tested\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Linked periostin to specific differentiation and developmental programs, showing it is required for osteoblast differentiation and is spatiotemporally expressed during cardiac morphogenesis.\",\n      \"evidence\": \"Antisense/antibody loss-of-function in osteoblasts and Northern/in situ hybridization in chick heart\",\n      \"pmids\": [\"15258926\", \"15532025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of differentiation control not defined\", \"Receptor and signaling pathway not identified\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identified upstream inducers in development, demonstrating BMP-2/BMPR-1B signaling drives periostin expression in cardiac cushion mesenchyme via Twist/Id1.\",\n      \"evidence\": \"Constitutively-active/dominant-negative viral constructs and noggin in chick AV cushion cells with qRT-PCR\",\n      \"pmids\": [\"18261719\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct promoter binding by Twist/Id1 not shown\", \"Downstream periostin function in cushion remodeling not tested here\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Showed periostin isoform PLF actively promotes bone formation, extending its role from differentiation marker to functional driver of osteoblast proliferation and fracture healing.\",\n      \"evidence\": \"Adenoviral overexpression in vitro and intramarrow injection in rat femur with mineralization assays\",\n      \"pmids\": [\"19006175\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Receptor/signaling mechanism unresolved\", \"Isoform-specific functions not dissected\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated a regulatory role in kidney organogenesis, with periostin inhibiting branching morphogenesis and co-expressing with its \\u03b1v integrin receptor.\",\n      \"evidence\": \"Metanephric explant culture with recombinant periostin, qRT-PCR and immunofluorescence co-localization\",\n      \"pmids\": [\"21855915\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct integrin signaling not functionally tested\", \"BMP-4 to periostin promoter link not established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Established periostin as a TGF-\\u03b21-induced effector of organ fibrosis and a pro-inflammatory/catabolic signaling ligand, central to its remodeling functions.\",\n      \"evidence\": \"Postn-knockout mice in CCl4/BDL liver fibrosis; recombinant periostin on chondrocytes with NF-\\u03baB inhibition; KO/gain-of-function in pancreatic regeneration and bone unloading\",\n      \"pmids\": [\"25541330\", \"26289167\", \"25485969\", \"25445447\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Surface receptor in fibrosis not pinned to a single integrin\", \"Whether periostin acts on stellate cells autonomously or via collagen scaffolding unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined a mechanotransduction circuit, showing compressive force induces POSTN through locally retained TGF-\\u03b21 rather than soluble signaling.\",\n      \"evidence\": \"Compressive loading of periodontal ligament fibroblasts with TGF-\\u03b2 inhibitor, neutralizing antibody and cycloheximide\",\n      \"pmids\": [\"25870205\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcription factors mediating force-induced POSTN not identified\", \"How matrix-retained TGF-\\u03b21 is activated by force unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified transcriptional and signaling regulators in cancer, placing POSTN as a direct TAp73 target and a STAT3-activating driver of glioma invasion and anti-angiogenic resistance.\",\n      \"evidence\": \"ChIP and luciferase reporter for TAp73; recombinant POSTN and xenograft analyses for STAT3/HIF1\\u03b1/VEGF\",\n      \"pmids\": [\"26930720\", \"27307601\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of STAT3 activation by POSTN not dissected\", \"Receptor mediating glioma effects not defined here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Consolidated the scaffold model and validated periostin as a therapeutic target, with its FAS1 domains organizing matrix proteins and RNA/antibody blockade reducing lung and kidney fibrosis.\",\n      \"evidence\": \"Domain-binding mapping syntheses; intranasal siRNA/antisense in bleomycin lung fibrosis; anti-periostin antibody, aptamer, and integrin-blockade peptide in renal fibrosis models\",\n      \"pmids\": [\"29086200\", \"28887577\", \"28820502\", \"29268247\", \"28819200\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Quantitative stoichiometry of scaffold assembly unknown\", \"Specific integrin engaged in each fibrotic tissue not fully resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Positioned periostin upstream of tumor stromal remodeling, showing it drives M2 macrophage and \\u03b1SMA+ stromal rebound and revascularization after anti-VEGFA therapy.\",\n      \"evidence\": \"Genetic Postn deletion in RIP1-Tag2 mice with VEGFA blockade and anti-CSF1R macrophage depletion\",\n      \"pmids\": [\"29514082\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Receptor by which POSTN recruits macrophages not identified\", \"Direct vs. matrix-mediated effect on stroma not separated\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified specific receptors and binding partners mediating periostin signaling, establishing integrin-\\u03b21 in renal repair/macrophage proliferation and tenascin-C as a direct interactor driving pathological angiogenesis.\",\n      \"evidence\": \"Conditional tubule Postn gain/loss mice with integrin-\\u03b21 interaction studies; Co-IP of periostin with tenascin-C plus siRNA and KO retinopathy models\",\n      \"pmids\": [\"31690575\", \"32518264\", \"30991832\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether integrin-\\u03b21 acts directly on macrophages or tubular cells in each context unclear\", \"Isoform-specific functional differences only partly characterized\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Mapped a network of receptors and downstream pathways across tissues, defining DDR1\\u2192AKT/\\u03b2-catenin for cartilage catabolism, integrin\\u03b21/RhoA for myofibroblast contraction, \\u03b1v\\u03b23/PI3K/Akt for tumor EMT, and feedback loops in angiogenesis, calcification, and autophagy.\",\n      \"evidence\": \"DDR1 KO chondrocytes; Postn-KO palatal fibroblasts with recombinant rescue and Rac inhibition; CAF \\u03b1v\\u03b23 co-culture; HIF-1\\u03b1/TrkB epistasis; NF-\\u03baB-ADAMTS5 and autophagy/ROS assays; pericyte 3D angiogenesis\",\n      \"pmids\": [\"32330138\", \"32777343\", \"33317907\", \"32752980\", \"31840212\", \"33744420\", \"32647861\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which receptor predominates when multiple are co-expressed not resolved\", \"How a single ligand selects divergent downstream pathways in different cells unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Established a complete receptor-to-transcription axis in glioma, showing POSTN drives stem-cell self-renewal via \\u03b1V\\u03b23/PI3K/AKT/\\u03b2-catenin/FOSL1 and immunosuppression via NF-\\u03baB/CD70.\",\n      \"evidence\": \"POSTN knockdown, ChIP-seq/ChIP-PCR for \\u03b2-catenin\\u2192FOSL1, tumorsphere and immunosuppression assays, orthotopic and patient-derived xenografts\",\n      \"pmids\": [\"39227950\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cellular source of POSTN within the niche not fully assigned\", \"Crosstalk between the two bifurcating pathways not explored\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended periostin into intracellular metabolic and epigenetic regulation, showing TGF-\\u03b2/Smad-induced periostin impairs cardiac BCAA catabolism through a NAP1L2/SIRT3/H3K27ac axis, and connecting CAF-derived periostin to collagen-alignment-driven lymphatic metastasis.\",\n      \"evidence\": \"RNA-seq guided KO/overexpression with H3K27ac ChIP and SIRT3 assays in diabetic cardiomyopathy; in vivo lineage tracing and ablation of periostin+ CAFs with collagen/invasion assays\",\n      \"pmids\": [\"37993768\", \"37205636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How a secreted matrix protein triggers intracellular NAP1L2 induction is mechanistically incomplete\", \"Generalizability of the lymphatic-specific metastasis effect to other tumors untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the mechanosensing machinery of periostin+ myofibroblasts, placing PIEZO1\\u2192Yap/Taz downstream of mechanical activation in lung fibrosis.\",\n      \"evidence\": \"Postn-Cre conditional Piezo1 and Yap/Taz deletion, cell ablation, actin imaging and bleomycin fibrosis model\",\n      \"pmids\": [\"40454481\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether periostin itself feeds into PIEZO1 activation not tested\", \"Relationship between secreted periostin and intracellular mechanotransduction unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unclear how a single matricellular ligand selects among its multiple receptors (integrin-\\u03b21, \\u03b1v\\u03b23, DDR1) and divergent downstream pathways in a cell- and context-specific manner, and how secreted periostin connects to its reported intracellular and mechanosensing functions.\",\n      \"evidence\": \"No single study in the corpus reconciles receptor selection or links extracellular periostin to intracellular signaling\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of receptor selectivity\", \"No unified accounting of extracellular vs. intracellular periostin actions\", \"Isoform-specific receptor preferences undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [19, 22, 23, 29]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [13, 14]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [13, 14, 25]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [13, 14, 31]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [13, 14, 25, 31]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [19, 22, 23, 29]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [6, 15, 17, 30]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2, 3, 4, 5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ITGB1\",\n      \"ITGAV\",\n      \"ITGB3\",\n      \"DDR1\",\n      \"TNC\",\n      \"FN1\",\n      \"BMP1\",\n      \"NOTCH1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}