{"gene":"POSTN","run_date":"2026-04-28T19:45:44","timeline":{"discoveries":[{"year":2014,"finding":"Periostin activates integrin α6β4 on hepatocytes, triggering JNK signaling pathway activation, which leads to c-Jun activation that prevents RORα binding at the Ppara promoter, thereby suppressing PPARα expression and promoting hepatic steatosis and hypertriglyceridemia.","method":"In vitro hepatocyte assays with integrin blockade, overexpression/knockout mouse models, neutralizing antibody, promoter binding studies","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including KO mice, neutralizing antibody, in vitro integrin blockade, and promoter studies in a single study","pmids":["25003192"],"is_preprint":false},{"year":2014,"finding":"Periostin binds to integrin receptors in valve progenitor cushion cells and activates focal adhesion kinase (FAK), PI3K/AKT, and ERK signaling pathways, promoting cell adhesion, migration, anti-apoptosis, collagen expression, and hyaluronan synthase-2 (Has2) activation during atrioventricular valvulogenesis.","method":"Explant cultures, gene transfection, Western blotting, functional assays with PN-null vs WT mice, 3D collagen compaction assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — reconstitution-style explant assays combined with KO mouse comparison and multiple pathway readouts","pmids":["24469446"],"is_preprint":false},{"year":2020,"finding":"Periostin interacts with integrin-β1 on tubular epithelial cells to inhibit cell cycle arrest and apoptosis after ischemia-reperfusion injury; periostin from overexpressing tubules directly induces macrophage proliferation and expression of proregenerative molecules.","method":"Conditional tubule-specific overexpression mice, periostin-KO mice, in vivo ischemia-reperfusion model, in vitro hypoxia-reoxygenation, co-culture of macrophages with recombinant periostin","journal":"Journal of the American Society of Nephrology : JASN","confidence":"High","confidence_rationale":"Tier 2 — gain- and loss-of-function in vivo plus in vitro recombinant protein mechanistic validation","pmids":["31690575"],"is_preprint":false},{"year":2016,"finding":"Fibrocyte-secreted periostin promotes myofibroblast differentiation via beta-1 integrin as its receptor on fibrocytes, and upregulates connective tissue growth factor (CTGF) and lysyl oxidase (LOX) mRNA in fibrocytes to augment pulmonary fibrosis.","method":"Conditioned medium experiments, adoptive transfer of WT vs periostin-/- fibrocytes, in vitro TGFβ1 and recombinant periostin treatment, bleomycin fibrosis model","journal":"Mucosal immunology","confidence":"High","confidence_rationale":"Tier 2 — adoptive transfer epistasis plus in vitro receptor identification and multiple readouts","pmids":["27435108"],"is_preprint":false},{"year":2020,"finding":"CAF-derived periostin functions as a ligand for integrin αvβ3, activating the PI3K/Akt pathway and inducing EMT to drive migration and invasion of ovarian cancer cells; TGF-β1-induced fibroblast activation partly relies on periostin upregulation.","method":"Lentiviral knockdown/overexpression, Transwell migration/invasion assays, RNA sequencing, Western blotting, indirect co-culture","journal":"Gynecologic oncology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods in single lab study with defined receptor and pathway","pmids":["33317907"],"is_preprint":false},{"year":2012,"finding":"Periostin promotes tumor lymphangiogenesis directly by stimulating tube formation of lymphatic endothelial cells (mediated by Src and Akt activity) and indirectly by upregulating VEGF-C mRNA expression in head and neck squamous cell carcinoma cells.","method":"Periostin overexpression in cancer cells, conditioned media tube formation assays with lymphatic endothelial cells, correlation with VEGF-C in HNSCC cases and serum, xenograft tumors","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2–3 — in vitro mechanistic assays with kinase inhibitors plus in vivo xenograft correlation","pmids":["22952986"],"is_preprint":false},{"year":2010,"finding":"TGF-β1 induces periostin expression in PDL fibroblasts via a focal adhesion kinase (FAK)-dependent pathway; cyclic mechanical strain also upregulates periostin mRNA through FAK, as FAK-null fibroblasts lack detectable periostin mRNA even under strain.","method":"Cyclic strain application to PDL fibroblasts, FAK inhibition, FAK-null fibroblasts, TGF-β1 treatment, qRT-PCR","journal":"Journal of dental research","confidence":"Medium","confidence_rationale":"Tier 2 — genetic (FAK-null) and pharmacological FAK inhibition with two stimuli converging on same endpoint","pmids":["20940356"],"is_preprint":false},{"year":2015,"finding":"Periostin promotes Rho-associated protein kinase (ROCK)-dependent proliferation and myofibroblast persistence in hypertrophic scar fibroblasts; matrix-associated periostin maintains high α-smooth muscle actin levels under reducing matrix tension, and ROCK inhibition attenuates these periostin effects.","method":"Recombinant periostin supplementation of collagen substrate, 3D collagen lattice contraction assays, ROCK inhibitor treatment, periostin siRNA knockdown in myofibroblasts","journal":"Experimental dermatology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple assays (proliferation, focal adhesion, collagen contraction, siRNA KD) with pharmacological pathway inhibition","pmids":["25421393"],"is_preprint":false},{"year":2020,"finding":"Periostin modulates myofibroblast differentiation and contraction via the integrin-β1/RhoA pathway, and regulates fibronectin synthesis in an ECM stiffness-dependent manner during palatal healing; periostin is required for formation of focal and fibrillar adhesions in palatal fibroblasts.","method":"Postn-/- knockout vs WT mice with palatal wounds, fibroblasts on silicon substrates of varying stiffness, collagen gel contraction, Rac inhibition rescue, immunostaining for vinculin and integrin-β1","journal":"Matrix biology : journal of the International Society for Matrix Biology","confidence":"Medium","confidence_rationale":"Tier 2 — KO mouse model combined with in vitro mechanical substrate assays and pharmacological pathway rescue","pmids":["32777343"],"is_preprint":false},{"year":2021,"finding":"A short periostin isoform (lacking exon 17, aa 22–669) expressed on the surface of CPC-derived exosomes promotes cardiomyocyte cell cycle re-entry by activating FAK phosphorylation, actin polymerization, and nuclear translocation of YAP; full-length recombinant periostin does not induce this proliferative effect, demonstrating isoform-specificity.","method":"Cryo-EM with immune-gold labeling, Western blot with isoform-specific antibodies, siRNA knockdown of periostin or YAP, FAK inhibitor (PF-573228), neonatal rat cardiomyocytes in vitro and in vivo after MI, human iPS-derived cardiomyocytes","journal":"Theranostics","confidence":"High","confidence_rationale":"Tier 1–2 — cryo-EM visualization, isoform-specific protein analysis, multiple cell types, genetic and pharmacological pathway blockade","pmids":["33897872"],"is_preprint":false},{"year":2020,"finding":"Periostin signals through discoidin domain receptor-1 (DDR1), a receptor tyrosine kinase, to induce collagen and proteoglycan degradation in chondrocytes via downstream MMP-13 and ADAMTS4 expression; genetic deficiency or pharmacological inhibition of DDR1 blocks periostin-induced MMP-13 expression.","method":"DDR1 KO mouse chondrocytes, DDR1 pharmacological inhibitor, in vitro periostin stimulation, MMP-13 expression readout","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — genetic and pharmacological DDR1 blockade converging on same pathway in single lab study","pmids":["32330138"],"is_preprint":false},{"year":2020,"finding":"Periostin induces IκBα phosphorylation and degradation leading to p65 nuclear translocation and ADAMTS5 upregulation in chondrocytes, mediating condylar resorption; NF-κB inhibition (BAY 11-7082) rescues periostin-induced ADAMTS5 upregulation.","method":"In vitro pressure-induced periostin expression in chondrocytes, Western blot for NF-κB pathway components, NF-κB inhibitor treatment, immunohistochemistry in TMJ-OA cartilage","journal":"Inflammation","confidence":"Medium","confidence_rationale":"Tier 2 — defined signaling cascade with pharmacological rescue in single lab study","pmids":["31840212"],"is_preprint":false},{"year":2020,"finding":"FAM20C (Golgi casein kinase) directly binds periostin through the Fasciclin I domains 1–4 and phosphorylates periostin in vitro; binding is kinase-activity-independent, and FAM20C and periostin co-localize in periodontal ligament extracellular matrix.","method":"Pulldown with WT and kinase-dead D478A FAM20C, mass spectrometry identification, in vitro binding assay, domain mapping, in vitro kinase assay, immunohistochemistry co-localization","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 — direct in vitro kinase assay with domain mapping and kinase-dead mutant controls","pmids":["33051588"],"is_preprint":false},{"year":2019,"finding":"Periostin overexpression in pulmonary hypertension activates HIF-1α, increasing ET-1 and VEGF production in endothelial cells; siRNA knockdown of HIF-1α abolishes the pro-angiogenic effect of periostin; TrkB (tyrosine kinase receptor B) mediates the effect of periostin on HIF-1α, and HIF-1α in turn drives POSTN expression, forming a positive feedback loop.","method":"siRNA knockdown of HIF-1α and POSTN in hPAECs, TrkB inhibition, POSTN overexpression, mouse PH models (Sugen 5416/hypoxia and chronic hypoxia), genetic epistasis","journal":"Circulation research","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis in human primary cells and animal models with multiple pathway interventions","pmids":["32752980"],"is_preprint":false},{"year":2000,"finding":"Periostin expression is regulated by Wnt-3 signaling through a beta-catenin-independent pathway; Wnt-3 infection and GSK-3 inhibition upregulate periostin, but beta-catenin overexpression or antisense knockdown has no effect on periostin expression in mouse mammary epithelial cells.","method":"Wnt-3 viral infection, GSK-3 inhibition, beta-catenin overexpression, beta-catenin antisense oligonucleotide, gene expression profiling","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple genetic perturbations defining beta-catenin-independent Wnt pathway regulation","pmids":["10884377"],"is_preprint":false},{"year":2015,"finding":"Intermittent compressive force increases POSTN (periostin) expression in human PDL fibroblasts via TGF-β1 signaling; TGF-β1 inhibition with SB431542 or TGF-β1 neutralizing antibody attenuates force-induced POSTN expression, and TGF-β1 accumulates intracellularly/in surrounding matrix (not secreted into medium) in response to force.","method":"Computerized compressive force loading apparatus, TGF-β1 inhibitor, neutralizing antibody, cycloheximide treatment, qRT-PCR, Western blot, ELISA","journal":"Journal of dental research","confidence":"Medium","confidence_rationale":"Tier 2 — pharmacological and antibody epistasis with two orthogonal readouts in single lab study","pmids":["25870205"],"is_preprint":false},{"year":2015,"finding":"Periostin promotes migration of Schwann cell precursors; periostin expression is induced by neuregulin-1 (NRG1, via ErbB receptors) and TGF-β1 in Schwann cells; DRG explant cultures from periostin-deficient mice show significantly reduced numbers of migrating Schwann cells.","method":"Comparative gene expression analysis of ErbB3-deficient vs WT DRG cultures, NRG1/TGFβ-1 stimulation, periostin-KO DRG explant cultures, migration quantification","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — genetic KO functional assay plus upstream regulator identification with two stimuli","pmids":["26187852"],"is_preprint":false},{"year":2014,"finding":"Periostin deficiency abrogates hepatic fibrosis in mice; periostin co-localizes with hepatic stellate cell-derived collagen I and α-SMA; TGF-β1 markedly induces periostin expression in primary mouse hepatic stellate cells; periostin-deficient mice show lower TGF-β1 and TGF-β2 levels after liver injury.","method":"Periostin-KO mice, carbon tetrachloride and bile duct ligation models, primary hepatic stellate cell cultures, immunohistochemistry co-localization, mRNA analysis","journal":"The American journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 — KO mouse model with in vitro primary cell mechanistic validation","pmids":["25541330"],"is_preprint":false},{"year":2019,"finding":"Periostin mediates EMT in hepatoblastoma through activation of the MAPK/ERK pathway, upregulating Snail and decreasing OVOL2 expression, thereby promoting migration and adhesion of HB cells.","method":"POSTN overexpression in HB cell lines, Western blot for ERK pathway and EMT markers, chemotaxis and cell-matrix adhesion assays","journal":"Cancer biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single overexpression approach with pathway readout but no pharmacological rescue or KO validation","pmids":["31119049"],"is_preprint":false},{"year":2014,"finding":"Periostin activates NF-κB signaling in epithelial cells and fibroblasts, constituting an epithelial/mesenchymal interaction important for chronic allergic inflammation in asthma and atopic dermatitis.","method":"Summarized from review citing original experimental work on NF-κB activation by periostin in fibroblasts and epithelial cells","journal":"Cellular and molecular life sciences : CMLS","confidence":"Low","confidence_rationale":"Tier 3 — cited as established in review without primary experimental detail in this abstract","pmids":["28887633"],"is_preprint":false},{"year":2020,"finding":"Periostin secreted by glioblastoma stem cells (GSCs) activates αVβ3 integrin to stimulate PI3K/AKT/β-catenin/FOSL1 pathway, promoting GSC self-renewal and tumor growth; additionally, GSC-derived periostin recruits microglia and upregulates CD70 on microglia via the αVβ3/PI3K/AKT/NF-κB pathway, driving Treg development and immunosuppression.","method":"POSTN depletion in GSCs, tumorsphere formation assays, ChIP-seq/ChIP-PCR for β-catenin binding to FOSL1 promoter, Transwell migration, T cell functional assays, patient-derived xenograft and orthotopic mouse models","journal":"Journal of experimental & clinical cancer research : CR","confidence":"High","confidence_rationale":"Tier 1–2 — ChIP-seq defines direct transcriptional target, multiple in vitro and in vivo mechanistic approaches with receptor and pathway specificity","pmids":["39227950"],"is_preprint":false},{"year":2023,"finding":"Hyperglycemia stimulates periostin expression in cardiac fibroblasts via TGF-β/Smad signaling; periostin upregulates NAP1L2, which recruits SIRT3 to deacetylate H3K27ac on the promoters of BCAA catabolism enzymes BCAT2 and PP2Cm, impairing BCAA catabolism and contributing to diabetic cardiomyopathy.","method":"RNA sequencing, gain/loss-of-function in diabetic mice and cardiac fibroblasts, TGF-β/Smad pathway inhibition, chromatin immunoprecipitation for H3K27ac, BCAT2/PP2Cm expression analysis, glucosyringic acid periostin inhibition","journal":"Cellular & molecular biology letters","confidence":"Medium","confidence_rationale":"Tier 2 — RNA-seq plus ChIP and pathway epistasis with pharmacological periostin inhibitor in single lab study","pmids":["37993768"],"is_preprint":false},{"year":2004,"finding":"Periostin acts as a cell adhesion molecule in cardiac development by binding to cell surface integrins; its expression is induced by TGF-beta and bone morphogenetic protein stimulation and is localized to developing ventricular trabeculae endothelium, outflow tract, and atrioventricular endocardial cushions.","method":"Northern analysis, whole mount and section in situ hybridization in chicken cardiac development, cloning of chicken periostin ortholog","journal":"The anatomical record","confidence":"Medium","confidence_rationale":"Tier 2 — direct expression mapping in defined developmental context with functional upstream regulators identified","pmids":["15532025"],"is_preprint":false},{"year":2014,"finding":"Periostin is required for maximal airway hyperresponsiveness and inflammation after house dust mite (HDM) sensitization; periostin on dendritic cells is required for maximal T-cell proliferation and IL-13 responses, and adoptive transfer of WT bone marrow-derived DCs restores allergic responses in periostin-null mice.","method":"Postn-/- mice, HDM sensitization/challenge model, periostin neutralizing antibody (OC-20) in C57BL/6 mice, DC adoptive transfer, T cell co-culture with DCs, airway responsiveness measurement","journal":"The Journal of allergy and clinical immunology","confidence":"High","confidence_rationale":"Tier 2 — KO mouse model, neutralizing antibody, and adoptive transfer epistasis providing convergent mechanistic evidence","pmids":["24996263"],"is_preprint":false},{"year":2017,"finding":"siRNA and antisense oligonucleotides against periostin administered intranasally reduce periostin, TGF-β1, collagen deposition, and lung fibrosis scores in bleomycin-induced pulmonary fibrosis mice, establishing periostin as a functional driver of lung fibrosis.","method":"Intranasal siRNA and antisense oligonucleotide delivery in bleomycin fibrosis mouse model, measurement of periostin, TGF-β1, collagen in airway fluid and tissue","journal":"Gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 — two RNA therapeutic approaches (siRNA and antisense) converging on same endpoint in vivo","pmids":["28820502"],"is_preprint":false},{"year":2025,"finding":"PIEZO1 is highly expressed in periostin+ (Postn+) pulmonary myofibroblasts and mediates mechanosensation for myofibroblast activation; conditional deletion of Piezo1 in Postn+ cells disrupts actin organization and prevents YAP/TAZ nuclear localization, shifting myofibroblasts to an apoptotic state and inhibiting lung fibrosis; myofibroblast-specific Yap/Taz deletion fully recapitulates Piezo1-KO protective phenotype.","method":"Postn-CreERT2 lineage tracing, conditional Piezo1 KO in Postn+ cells, Yap/Taz conditional KO, bleomycin fibrosis model, actin organization and YAP/TAZ nuclear localization assays","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1–2 — cell-type-specific conditional KO of both Piezo1 and Yap/Taz with epistasis and cellular phenotype readouts","pmids":["40454481"],"is_preprint":false}],"current_model":"Periostin is a secreted matricellular protein that functions primarily through binding to integrin receptors (αvβ3, αvβ5, α6β4, β1) to activate downstream signaling cascades including FAK, PI3K/AKT, ERK/MAPK, and NF-κB, thereby regulating cell adhesion, migration, survival, myofibroblast differentiation, collagen fibrillogenesis, and tissue remodeling; its expression is induced by TGF-β/Smad, Wnt-3 (beta-catenin-independent), HIF-1α, IL-4/IL-13, and mechanical stress, and it is phosphorylated by the Golgi kinase FAM20C; isoform-specific functions have been identified, including a short exon-17-lacking isoform on exosome surfaces that drives cardiomyocyte proliferation via FAK/YAP, whereas full-length periostin does not, and PIEZO1-mediated mechanosensation in periostin-expressing myofibroblasts drives YAP/TAZ nuclear localization to sustain fibrotic activation."},"narrative":{"teleology":[{"year":2000,"claim":"Identification of the upstream Wnt pathway controlling POSTN expression resolved whether its regulation involved canonical β-catenin signaling, establishing that Wnt-3 induces periostin through a β-catenin-independent mechanism.","evidence":"Wnt-3 viral infection, GSK-3 inhibition, and β-catenin overexpression/antisense in mouse mammary epithelial cells","pmids":["10884377"],"confidence":"Medium","gaps":["Downstream effectors of the non-canonical Wnt branch driving POSTN remain unidentified","Not tested in mesenchymal cell types where periostin is most abundant"]},{"year":2004,"claim":"Mapping periostin expression to developing cardiac cushions and trabeculae, with induction by TGF-β and BMP, established it as an integrin-binding matricellular factor in heart morphogenesis.","evidence":"In situ hybridization and Northern analysis in chick cardiac development","pmids":["15532025"],"confidence":"Medium","gaps":["No loss-of-function data at this stage","Specific integrin partners in cardiac tissue not identified"]},{"year":2010,"claim":"Demonstrating that both TGF-β1 and mechanical strain converge on FAK to induce periostin expression answered how mechanical loading is transduced to matrix remodeling gene programs.","evidence":"Cyclic strain on PDL fibroblasts with FAK inhibition and FAK-null fibroblasts","pmids":["20940356"],"confidence":"Medium","gaps":["FAK-dependent transcription factor mediating POSTN induction not identified","Tested only in periodontal ligament fibroblasts"]},{"year":2012,"claim":"Showing that periostin promotes lymphangiogenesis via Src/Akt activation and VEGF-C upregulation extended its functional repertoire beyond matrix adhesion to vascular remodeling in tumors.","evidence":"Conditioned media tube formation assays with kinase inhibitors and xenograft correlation in HNSCC","pmids":["22952986"],"confidence":"Medium","gaps":["Receptor on lymphatic endothelial cells not defined","No genetic loss-of-function in vivo"]},{"year":2014,"claim":"Multiple studies defined the specific integrin–effector cascades through which periostin acts: α6β4/JNK suppresses PPARα in hepatocytes causing steatosis; integrins/FAK/PI3K/AKT/ERK drive valvulogenesis; and periostin on dendritic cells is required for maximal allergic airway inflammation.","evidence":"KO mice, neutralizing antibodies, integrin blockade, explant cultures in liver, heart, and airway models; DC adoptive transfer restoring allergic responses in Postn−/− mice","pmids":["25003192","24469446","24996263"],"confidence":"High","gaps":["How periostin selectively engages different integrin heterodimers in different tissues is unknown","Structural basis for integrin selectivity not resolved"]},{"year":2015,"claim":"Periostin was shown to sustain myofibroblast persistence via ROCK-dependent proliferation and α-SMA maintenance, and its expression under compressive force was confirmed to require TGF-β1 signaling, linking mechanical loading to fibrotic matrix remodeling.","evidence":"3D collagen contraction with ROCK inhibitor in scar fibroblasts; compressive force apparatus with TGF-β1 inhibitor/neutralizing antibody in PDL fibroblasts; Schwann cell migration assays in Postn-KO DRG explants","pmids":["25421393","25870205","26187852"],"confidence":"Medium","gaps":["Whether ROCK activation is integrin-dependent not tested directly","Periostin's role in nerve repair beyond Schwann cell migration not explored"]},{"year":2016,"claim":"Demonstrating that fibrocyte-secreted periostin drives myofibroblast differentiation via β1-integrin and upregulates CTGF and LOX established periostin as a paracrine amplifier of pulmonary fibrosis.","evidence":"Adoptive transfer of WT vs Postn−/− fibrocytes in bleomycin model with in vitro receptor identification","pmids":["27435108"],"confidence":"High","gaps":["Downstream signaling from β1-integrin to CTGF/LOX transcription not dissected","Relevance to human IPF fibrosis not directly demonstrated"]},{"year":2020,"claim":"A burst of studies in 2020 extended periostin signaling to new receptors (DDR1 in chondrocytes), new effectors (NF-κB/ADAMTS5 in cartilage resorption, integrin-β1/RhoA in palatal wound healing), renal protection (integrin-β1 on tubular cells inhibiting apoptosis and promoting macrophage proliferation), and tumor immunosuppression (αvβ3/PI3K/AKT/NF-κB recruiting immunosuppressive microglia in glioblastoma).","evidence":"DDR1-KO chondrocytes and pharmacological inhibition; NF-κB inhibitor rescue; Postn−/− palatal wound model; conditional tubule-specific overexpression and Postn-KO in renal IRI; POSTN-depleted GSCs with ChIP-seq, tumorsphere assays, and orthotopic xenografts","pmids":["32330138","31840212","32777343","31690575","39227950"],"confidence":"High","gaps":["DDR1 as a periostin receptor has not been confirmed by direct binding assay","Whether NF-κB activation in tumors versus cartilage uses the same receptor is unknown","Relative contribution of autocrine versus paracrine periostin in GBM niche not resolved"]},{"year":2020,"claim":"Discovery of a HIF-1α–periostin positive feedback loop via TrkB in pulmonary hypertension revealed how periostin self-amplifies its own expression in hypoxic vascular disease, also linking to ET-1 and VEGF production.","evidence":"siRNA knockdown epistasis of HIF-1α, POSTN, and TrkB in hPAECs; Sugen/hypoxia and chronic hypoxia mouse PH models","pmids":["32752980"],"confidence":"Medium","gaps":["Direct physical interaction between periostin and TrkB not demonstrated","Whether this feedback loop operates in other hypoxic tissues is untested"]},{"year":2020,"claim":"Identification of FAM20C as a direct kinase that phosphorylates periostin Fasciclin I domains provided the first post-translational modification mechanism, showing that the interaction is kinase-activity-independent for binding but required for phosphorylation.","evidence":"In vitro kinase assay with WT and kinase-dead D478A FAM20C, domain mapping pulldown, co-localization in PDL ECM","pmids":["33051588"],"confidence":"High","gaps":["Phosphorylation sites on periostin not mapped","Functional consequence of FAM20C-mediated phosphorylation on periostin activity unknown"]},{"year":2021,"claim":"Demonstrating that a short periostin isoform (lacking exon 17) on exosome surfaces—but not full-length periostin—drives cardiomyocyte cell-cycle re-entry via FAK/YAP established the first clear isoform-specific function.","evidence":"Cryo-EM immune-gold labeling, isoform-specific antibodies, FAK inhibitor, YAP siRNA, neonatal rat and human iPSC-derived cardiomyocytes in vitro and in vivo post-MI","pmids":["33897872"],"confidence":"High","gaps":["Mechanism by which exon 17 deletion alters integrin engagement or FAK activation is unknown","Whether this isoform is generated by regulated alternative splicing or constitutive remains unclear"]},{"year":2023,"claim":"Periostin was linked to metabolic regulation via TGF-β/Smad-induced NAP1L2 upregulation, which recruits SIRT3 to deacetylate H3K27ac at BCAA catabolism gene promoters, connecting periostin to diabetic cardiomyopathy through impaired branched-chain amino acid metabolism.","evidence":"RNA-seq, ChIP for H3K27ac, gain/loss-of-function in diabetic mice and cardiac fibroblasts, TGF-β pathway inhibition","pmids":["37993768"],"confidence":"Medium","gaps":["Whether periostin-NAP1L2 axis operates outside the diabetic heart is untested","Direct paracrine effect of fibroblast-derived periostin on cardiomyocyte BCAA metabolism not shown"]},{"year":2025,"claim":"Conditional deletion of PIEZO1 in periostin-expressing myofibroblasts revealed that mechanosensation through PIEZO1 is required for YAP/TAZ nuclear localization and sustained fibrotic activation, with Yap/Taz deletion fully phenocopying PIEZO1 loss, placing PIEZO1 upstream of YAP/TAZ in periostin-lineage cells.","evidence":"Postn-CreERT2 lineage tracing, conditional Piezo1 KO and Yap/Taz double KO in Postn+ cells, bleomycin fibrosis model","pmids":["40454481"],"confidence":"High","gaps":["Whether PIEZO1 signals through integrins or independently of periostin-integrin axis is unresolved","Applicability to non-pulmonary fibrotic organs not tested"]},{"year":null,"claim":"Key unresolved questions include: the structural basis for isoform-specific and tissue-specific integrin engagement; the identity and functional consequences of FAM20C phosphorylation sites; and how periostin coordinates its distinct roles in fibrosis, immunity, and tumor immunosuppression at the single-cell level.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal structure of periostin bound to any integrin","Phosphosite mapping and functional phosphomutant studies lacking","Single-cell resolution of periostin paracrine circuits not yet achieved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[1,2,22]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[0,1,4,20]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,7,8,25]}],"localization":[{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[8,12,22]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,3,4,20]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1,4,5,11,20]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[3,8,17,24]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,16,22]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[20,23]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,4,13,18]}],"complexes":[],"partners":["ITGB1","ITGAV","ITGB3","ITGA6","ITGB4","FAM20C","DDR1","YAP1"],"other_free_text":[]},"mechanistic_narrative":"Periostin (POSTN) is a secreted matricellular protein that orchestrates cell adhesion, migration, survival, myofibroblast differentiation, and extracellular matrix remodeling across developmental, fibrotic, immune, and neoplastic contexts. It signals primarily through integrin receptors (αvβ3, α6β4, β1) to activate FAK, PI3K/AKT, ERK/MAPK, NF-κB, and Rho/ROCK cascades, thereby controlling processes ranging from atrioventricular valvulogenesis and collagen fibrillogenesis to epithelial-mesenchymal transition and tumor-associated immunosuppression [PMID:24469446, PMID:25003192, PMID:39227950, PMID:25421393]. Its expression is induced by TGF-β/Smad signaling, mechanical stress, Wnt-3 (β-catenin-independent), and HIF-1α, and the protein is phosphorylated extracellularly by the Golgi kinase FAM20C on its Fasciclin I domains [PMID:20940356, PMID:25870205, PMID:10884377, PMID:32752980, PMID:33051588]. Isoform-specific functions are functionally significant: a short exon-17-lacking isoform on exosome surfaces activates FAK/YAP to drive cardiomyocyte proliferation, whereas full-length periostin does not, and in periostin-expressing pulmonary myofibroblasts PIEZO1-mediated mechanosensation sustains fibrotic activation through YAP/TAZ nuclear localization [PMID:33897872, PMID:40454481]."},"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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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":17,"is_preprint":false},{"pmid":"33083453","id":"PMC_33083453","title":"miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/33083453","citation_count":17,"is_preprint":false},{"pmid":"29805541","id":"PMC_29805541","title":"Expression and clinical significance of periostin in oral lichen planus.","date":"2018","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/29805541","citation_count":17,"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":16,"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":16,"is_preprint":false},{"pmid":"29418037","id":"PMC_29418037","title":"Constitutive overexpression of periostin delays wound healing in mouse skin.","date":"2018","source":"Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society","url":"https://pubmed.ncbi.nlm.nih.gov/29418037","citation_count":16,"is_preprint":false},{"pmid":"25674935","id":"PMC_25674935","title":"Expression of POSTN, IL-4, and IL-13 in Chronic Rhinosinusitis with Nasal Polyps.","date":"2015","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25674935","citation_count":15,"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":14,"is_preprint":false},{"pmid":"33051588","id":"PMC_33051588","title":"FAM20C directly binds to and phosphorylates Periostin.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33051588","citation_count":14,"is_preprint":false},{"pmid":"25755133","id":"PMC_25755133","title":"Expression of Periostin in Normal, Atopic, and Nonatopic Chronically Inflamed Canine Skin.","date":"2015","source":"Veterinary pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25755133","citation_count":14,"is_preprint":false},{"pmid":"28913545","id":"PMC_28913545","title":"Periostin in vitreoretinal diseases.","date":"2017","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/28913545","citation_count":14,"is_preprint":false},{"pmid":"28965986","id":"PMC_28965986","title":"Deficiency of periostin impairs liver regeneration in mice after partial hepatectomy.","date":"2017","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/28965986","citation_count":14,"is_preprint":false},{"pmid":"39377227","id":"PMC_39377227","title":"Identification of Postn+ periosteal progenitor cells with bone regenerative potential.","date":"2024","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/39377227","citation_count":13,"is_preprint":false},{"pmid":"33141273","id":"PMC_33141273","title":"Effect of periostin silencing on Runx2, RANKL and OPG expression in osteoblasts.","date":"2020","source":"Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie","url":"https://pubmed.ncbi.nlm.nih.gov/33141273","citation_count":13,"is_preprint":false},{"pmid":"20083223","id":"PMC_20083223","title":"Periostin expression distinguishes between light and dark hypertrophic chondrocytes.","date":"2010","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20083223","citation_count":13,"is_preprint":false},{"pmid":"31037635","id":"PMC_31037635","title":"Role of Periostin in Cardiac Valve Development.","date":"2019","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/31037635","citation_count":12,"is_preprint":false},{"pmid":"34004251","id":"PMC_34004251","title":"MicroRNA-489-3p promotes adipogenesis by targeting the Postn gene in 3T3-L1 preadipocytes.","date":"2021","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34004251","citation_count":12,"is_preprint":false},{"pmid":"25757150","id":"PMC_25757150","title":"The expression of periostin in dental pulp cells.","date":"2015","source":"Archives of oral biology","url":"https://pubmed.ncbi.nlm.nih.gov/25757150","citation_count":12,"is_preprint":false},{"pmid":"32416542","id":"PMC_32416542","title":"Integrative Analysis of Periostin in Primary and Advanced Prostate Cancer.","date":"2020","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32416542","citation_count":12,"is_preprint":false},{"pmid":"35125949","id":"PMC_35125949","title":"The role of periostin in kidney diseases.","date":"2021","source":"Central-European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35125949","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46337,"output_tokens":6455,"usd":0.117918},"stage2":{"model":"claude-opus-4-6","input_tokens":10262,"output_tokens":3779,"usd":0.218677},"total_usd":0.336595,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin activates integrin α6β4 on hepatocytes, triggering JNK signaling pathway activation, which leads to c-Jun activation that prevents RORα binding at the Ppara promoter, thereby suppressing PPARα expression and promoting hepatic steatosis and hypertriglyceridemia.\",\n      \"method\": \"In vitro hepatocyte assays with integrin blockade, overexpression/knockout mouse models, neutralizing antibody, promoter binding studies\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including KO mice, neutralizing antibody, in vitro integrin blockade, and promoter studies in a single study\",\n      \"pmids\": [\"25003192\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin binds to integrin receptors in valve progenitor cushion cells and activates focal adhesion kinase (FAK), PI3K/AKT, and ERK signaling pathways, promoting cell adhesion, migration, anti-apoptosis, collagen expression, and hyaluronan synthase-2 (Has2) activation during atrioventricular valvulogenesis.\",\n      \"method\": \"Explant cultures, gene transfection, Western blotting, functional assays with PN-null vs WT mice, 3D collagen compaction assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstitution-style explant assays combined with KO mouse comparison and multiple pathway readouts\",\n      \"pmids\": [\"24469446\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin interacts with integrin-β1 on tubular epithelial cells to inhibit cell cycle arrest and apoptosis after ischemia-reperfusion injury; periostin from overexpressing tubules directly induces macrophage proliferation and expression of proregenerative molecules.\",\n      \"method\": \"Conditional tubule-specific overexpression mice, periostin-KO mice, in vivo ischemia-reperfusion model, in vitro hypoxia-reoxygenation, co-culture of macrophages with recombinant periostin\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — gain- and loss-of-function in vivo plus in vitro recombinant protein mechanistic validation\",\n      \"pmids\": [\"31690575\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Fibrocyte-secreted periostin promotes myofibroblast differentiation via beta-1 integrin as its receptor on fibrocytes, and upregulates connective tissue growth factor (CTGF) and lysyl oxidase (LOX) mRNA in fibrocytes to augment pulmonary fibrosis.\",\n      \"method\": \"Conditioned medium experiments, adoptive transfer of WT vs periostin-/- fibrocytes, in vitro TGFβ1 and recombinant periostin treatment, bleomycin fibrosis model\",\n      \"journal\": \"Mucosal immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — adoptive transfer epistasis plus in vitro receptor identification and multiple readouts\",\n      \"pmids\": [\"27435108\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CAF-derived periostin functions as a ligand for integrin αvβ3, activating the PI3K/Akt pathway and inducing EMT to drive migration and invasion of ovarian cancer cells; TGF-β1-induced fibroblast activation partly relies on periostin upregulation.\",\n      \"method\": \"Lentiviral knockdown/overexpression, Transwell migration/invasion assays, RNA sequencing, Western blotting, indirect co-culture\",\n      \"journal\": \"Gynecologic oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods in single lab study with defined receptor and pathway\",\n      \"pmids\": [\"33317907\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Periostin promotes tumor lymphangiogenesis directly by stimulating tube formation of lymphatic endothelial cells (mediated by Src and Akt activity) and indirectly by upregulating VEGF-C mRNA expression in head and neck squamous cell carcinoma cells.\",\n      \"method\": \"Periostin overexpression in cancer cells, conditioned media tube formation assays with lymphatic endothelial cells, correlation with VEGF-C in HNSCC cases and serum, xenograft tumors\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — in vitro mechanistic assays with kinase inhibitors plus in vivo xenograft correlation\",\n      \"pmids\": [\"22952986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"TGF-β1 induces periostin expression in PDL fibroblasts via a focal adhesion kinase (FAK)-dependent pathway; cyclic mechanical strain also upregulates periostin mRNA through FAK, as FAK-null fibroblasts lack detectable periostin mRNA even under strain.\",\n      \"method\": \"Cyclic strain application to PDL fibroblasts, FAK inhibition, FAK-null fibroblasts, TGF-β1 treatment, qRT-PCR\",\n      \"journal\": \"Journal of dental research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic (FAK-null) and pharmacological FAK inhibition with two stimuli converging on same endpoint\",\n      \"pmids\": [\"20940356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Periostin promotes Rho-associated protein kinase (ROCK)-dependent proliferation and myofibroblast persistence in hypertrophic scar fibroblasts; matrix-associated periostin maintains high α-smooth muscle actin levels under reducing matrix tension, and ROCK inhibition attenuates these periostin effects.\",\n      \"method\": \"Recombinant periostin supplementation of collagen substrate, 3D collagen lattice contraction assays, ROCK inhibitor treatment, periostin siRNA knockdown in myofibroblasts\",\n      \"journal\": \"Experimental dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple assays (proliferation, focal adhesion, collagen contraction, siRNA KD) with pharmacological pathway inhibition\",\n      \"pmids\": [\"25421393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin modulates myofibroblast differentiation and contraction via the integrin-β1/RhoA pathway, and regulates fibronectin synthesis in an ECM stiffness-dependent manner during palatal healing; periostin is required for formation of focal and fibrillar adhesions in palatal fibroblasts.\",\n      \"method\": \"Postn-/- knockout vs WT mice with palatal wounds, fibroblasts on silicon substrates of varying stiffness, collagen gel contraction, Rac inhibition rescue, immunostaining for vinculin and integrin-β1\",\n      \"journal\": \"Matrix biology : journal of the International Society for Matrix Biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse model combined with in vitro mechanical substrate assays and pharmacological pathway rescue\",\n      \"pmids\": [\"32777343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A short periostin isoform (lacking exon 17, aa 22–669) expressed on the surface of CPC-derived exosomes promotes cardiomyocyte cell cycle re-entry by activating FAK phosphorylation, actin polymerization, and nuclear translocation of YAP; full-length recombinant periostin does not induce this proliferative effect, demonstrating isoform-specificity.\",\n      \"method\": \"Cryo-EM with immune-gold labeling, Western blot with isoform-specific antibodies, siRNA knockdown of periostin or YAP, FAK inhibitor (PF-573228), neonatal rat cardiomyocytes in vitro and in vivo after MI, human iPS-derived cardiomyocytes\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — cryo-EM visualization, isoform-specific protein analysis, multiple cell types, genetic and pharmacological pathway blockade\",\n      \"pmids\": [\"33897872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin signals through discoidin domain receptor-1 (DDR1), a receptor tyrosine kinase, to induce collagen and proteoglycan degradation in chondrocytes via downstream MMP-13 and ADAMTS4 expression; genetic deficiency or pharmacological inhibition of DDR1 blocks periostin-induced MMP-13 expression.\",\n      \"method\": \"DDR1 KO mouse chondrocytes, DDR1 pharmacological inhibitor, in vitro periostin stimulation, MMP-13 expression readout\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic and pharmacological DDR1 blockade converging on same pathway in single lab study\",\n      \"pmids\": [\"32330138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin induces IκBα phosphorylation and degradation leading to p65 nuclear translocation and ADAMTS5 upregulation in chondrocytes, mediating condylar resorption; NF-κB inhibition (BAY 11-7082) rescues periostin-induced ADAMTS5 upregulation.\",\n      \"method\": \"In vitro pressure-induced periostin expression in chondrocytes, Western blot for NF-κB pathway components, NF-κB inhibitor treatment, immunohistochemistry in TMJ-OA cartilage\",\n      \"journal\": \"Inflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined signaling cascade with pharmacological rescue in single lab study\",\n      \"pmids\": [\"31840212\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"FAM20C (Golgi casein kinase) directly binds periostin through the Fasciclin I domains 1–4 and phosphorylates periostin in vitro; binding is kinase-activity-independent, and FAM20C and periostin co-localize in periodontal ligament extracellular matrix.\",\n      \"method\": \"Pulldown with WT and kinase-dead D478A FAM20C, mass spectrometry identification, in vitro binding assay, domain mapping, in vitro kinase assay, immunohistochemistry co-localization\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct in vitro kinase assay with domain mapping and kinase-dead mutant controls\",\n      \"pmids\": [\"33051588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Periostin overexpression in pulmonary hypertension activates HIF-1α, increasing ET-1 and VEGF production in endothelial cells; siRNA knockdown of HIF-1α abolishes the pro-angiogenic effect of periostin; TrkB (tyrosine kinase receptor B) mediates the effect of periostin on HIF-1α, and HIF-1α in turn drives POSTN expression, forming a positive feedback loop.\",\n      \"method\": \"siRNA knockdown of HIF-1α and POSTN in hPAECs, TrkB inhibition, POSTN overexpression, mouse PH models (Sugen 5416/hypoxia and chronic hypoxia), genetic epistasis\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis in human primary cells and animal models with multiple pathway interventions\",\n      \"pmids\": [\"32752980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Periostin expression is regulated by Wnt-3 signaling through a beta-catenin-independent pathway; Wnt-3 infection and GSK-3 inhibition upregulate periostin, but beta-catenin overexpression or antisense knockdown has no effect on periostin expression in mouse mammary epithelial cells.\",\n      \"method\": \"Wnt-3 viral infection, GSK-3 inhibition, beta-catenin overexpression, beta-catenin antisense oligonucleotide, gene expression profiling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple genetic perturbations defining beta-catenin-independent Wnt pathway regulation\",\n      \"pmids\": [\"10884377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Intermittent compressive force increases POSTN (periostin) expression in human PDL fibroblasts via TGF-β1 signaling; TGF-β1 inhibition with SB431542 or TGF-β1 neutralizing antibody attenuates force-induced POSTN expression, and TGF-β1 accumulates intracellularly/in surrounding matrix (not secreted into medium) in response to force.\",\n      \"method\": \"Computerized compressive force loading apparatus, TGF-β1 inhibitor, neutralizing antibody, cycloheximide treatment, qRT-PCR, Western blot, ELISA\",\n      \"journal\": \"Journal of dental research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pharmacological and antibody epistasis with two orthogonal readouts in single lab study\",\n      \"pmids\": [\"25870205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Periostin promotes migration of Schwann cell precursors; periostin expression is induced by neuregulin-1 (NRG1, via ErbB receptors) and TGF-β1 in Schwann cells; DRG explant cultures from periostin-deficient mice show significantly reduced numbers of migrating Schwann cells.\",\n      \"method\": \"Comparative gene expression analysis of ErbB3-deficient vs WT DRG cultures, NRG1/TGFβ-1 stimulation, periostin-KO DRG explant cultures, migration quantification\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO functional assay plus upstream regulator identification with two stimuli\",\n      \"pmids\": [\"26187852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin deficiency abrogates hepatic fibrosis in mice; periostin co-localizes with hepatic stellate cell-derived collagen I and α-SMA; TGF-β1 markedly induces periostin expression in primary mouse hepatic stellate cells; periostin-deficient mice show lower TGF-β1 and TGF-β2 levels after liver injury.\",\n      \"method\": \"Periostin-KO mice, carbon tetrachloride and bile duct ligation models, primary hepatic stellate cell cultures, immunohistochemistry co-localization, mRNA analysis\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse model with in vitro primary cell mechanistic validation\",\n      \"pmids\": [\"25541330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Periostin mediates EMT in hepatoblastoma through activation of the MAPK/ERK pathway, upregulating Snail and decreasing OVOL2 expression, thereby promoting migration and adhesion of HB cells.\",\n      \"method\": \"POSTN overexpression in HB cell lines, Western blot for ERK pathway and EMT markers, chemotaxis and cell-matrix adhesion assays\",\n      \"journal\": \"Cancer biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single overexpression approach with pathway readout but no pharmacological rescue or KO validation\",\n      \"pmids\": [\"31119049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin activates NF-κB signaling in epithelial cells and fibroblasts, constituting an epithelial/mesenchymal interaction important for chronic allergic inflammation in asthma and atopic dermatitis.\",\n      \"method\": \"Summarized from review citing original experimental work on NF-κB activation by periostin in fibroblasts and epithelial cells\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — cited as established in review without primary experimental detail in this abstract\",\n      \"pmids\": [\"28887633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Periostin secreted by glioblastoma stem cells (GSCs) activates αVβ3 integrin to stimulate PI3K/AKT/β-catenin/FOSL1 pathway, promoting GSC self-renewal and tumor growth; additionally, GSC-derived periostin recruits microglia and upregulates CD70 on microglia via the αVβ3/PI3K/AKT/NF-κB pathway, driving Treg development and immunosuppression.\",\n      \"method\": \"POSTN depletion in GSCs, tumorsphere formation assays, ChIP-seq/ChIP-PCR for β-catenin binding to FOSL1 promoter, Transwell migration, T cell functional assays, patient-derived xenograft and orthotopic mouse models\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — ChIP-seq defines direct transcriptional target, multiple in vitro and in vivo mechanistic approaches with receptor and pathway specificity\",\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 signaling; periostin upregulates NAP1L2, which recruits SIRT3 to deacetylate H3K27ac on the promoters of BCAA catabolism enzymes BCAT2 and PP2Cm, impairing BCAA catabolism and contributing to diabetic cardiomyopathy.\",\n      \"method\": \"RNA sequencing, gain/loss-of-function in diabetic mice and cardiac fibroblasts, TGF-β/Smad pathway inhibition, chromatin immunoprecipitation for H3K27ac, BCAT2/PP2Cm expression analysis, glucosyringic acid periostin inhibition\",\n      \"journal\": \"Cellular & molecular biology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RNA-seq plus ChIP and pathway epistasis with pharmacological periostin inhibitor in single lab study\",\n      \"pmids\": [\"37993768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Periostin acts as a cell adhesion molecule in cardiac development by binding to cell surface integrins; its expression is induced by TGF-beta and bone morphogenetic protein stimulation and is localized to developing ventricular trabeculae endothelium, outflow tract, and atrioventricular endocardial cushions.\",\n      \"method\": \"Northern analysis, whole mount and section in situ hybridization in chicken cardiac development, cloning of chicken periostin ortholog\",\n      \"journal\": \"The anatomical record\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct expression mapping in defined developmental context with functional upstream regulators identified\",\n      \"pmids\": [\"15532025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Periostin is required for maximal airway hyperresponsiveness and inflammation after house dust mite (HDM) sensitization; periostin on dendritic cells is required for maximal T-cell proliferation and IL-13 responses, and adoptive transfer of WT bone marrow-derived DCs restores allergic responses in periostin-null mice.\",\n      \"method\": \"Postn-/- mice, HDM sensitization/challenge model, periostin neutralizing antibody (OC-20) in C57BL/6 mice, DC adoptive transfer, T cell co-culture with DCs, airway responsiveness measurement\",\n      \"journal\": \"The Journal of allergy and clinical immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse model, neutralizing antibody, and adoptive transfer epistasis providing convergent mechanistic evidence\",\n      \"pmids\": [\"24996263\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"siRNA and antisense oligonucleotides against periostin administered intranasally reduce periostin, TGF-β1, collagen deposition, and lung fibrosis scores in bleomycin-induced pulmonary fibrosis mice, establishing periostin as a functional driver of lung fibrosis.\",\n      \"method\": \"Intranasal siRNA and antisense oligonucleotide delivery in bleomycin fibrosis mouse model, measurement of periostin, TGF-β1, collagen in airway fluid and tissue\",\n      \"journal\": \"Gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — two RNA therapeutic approaches (siRNA and antisense) converging on same endpoint in vivo\",\n      \"pmids\": [\"28820502\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PIEZO1 is highly expressed in periostin+ (Postn+) pulmonary myofibroblasts and mediates mechanosensation for myofibroblast activation; conditional deletion of Piezo1 in Postn+ cells disrupts actin organization and prevents YAP/TAZ nuclear localization, shifting myofibroblasts to an apoptotic state and inhibiting lung fibrosis; myofibroblast-specific Yap/Taz deletion fully recapitulates Piezo1-KO protective phenotype.\",\n      \"method\": \"Postn-CreERT2 lineage tracing, conditional Piezo1 KO in Postn+ cells, Yap/Taz conditional KO, bleomycin fibrosis model, actin organization and YAP/TAZ nuclear localization assays\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — cell-type-specific conditional KO of both Piezo1 and Yap/Taz with epistasis and cellular phenotype readouts\",\n      \"pmids\": [\"40454481\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Periostin is a secreted matricellular protein that functions primarily through binding to integrin receptors (αvβ3, αvβ5, α6β4, β1) to activate downstream signaling cascades including FAK, PI3K/AKT, ERK/MAPK, and NF-κB, thereby regulating cell adhesion, migration, survival, myofibroblast differentiation, collagen fibrillogenesis, and tissue remodeling; its expression is induced by TGF-β/Smad, Wnt-3 (beta-catenin-independent), HIF-1α, IL-4/IL-13, and mechanical stress, and it is phosphorylated by the Golgi kinase FAM20C; isoform-specific functions have been identified, including a short exon-17-lacking isoform on exosome surfaces that drives cardiomyocyte proliferation via FAK/YAP, whereas full-length periostin does not, and PIEZO1-mediated mechanosensation in periostin-expressing myofibroblasts drives YAP/TAZ nuclear localization to sustain fibrotic activation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"Periostin (POSTN) is a secreted matricellular protein that orchestrates cell adhesion, migration, survival, myofibroblast differentiation, and extracellular matrix remodeling across developmental, fibrotic, immune, and neoplastic contexts. It signals primarily through integrin receptors (αvβ3, α6β4, β1) to activate FAK, PI3K/AKT, ERK/MAPK, NF-κB, and Rho/ROCK cascades, thereby controlling processes ranging from atrioventricular valvulogenesis and collagen fibrillogenesis to epithelial-mesenchymal transition and tumor-associated immunosuppression [PMID:24469446, PMID:25003192, PMID:39227950, PMID:25421393]. Its expression is induced by TGF-β/Smad signaling, mechanical stress, Wnt-3 (β-catenin-independent), and HIF-1α, and the protein is phosphorylated extracellularly by the Golgi kinase FAM20C on its Fasciclin I domains [PMID:20940356, PMID:25870205, PMID:10884377, PMID:32752980, PMID:33051588]. Isoform-specific functions are functionally significant: a short exon-17-lacking isoform on exosome surfaces activates FAK/YAP to drive cardiomyocyte proliferation, whereas full-length periostin does not, and in periostin-expressing pulmonary myofibroblasts PIEZO1-mediated mechanosensation sustains fibrotic activation through YAP/TAZ nuclear localization [PMID:33897872, PMID:40454481].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Identification of the upstream Wnt pathway controlling POSTN expression resolved whether its regulation involved canonical β-catenin signaling, establishing that Wnt-3 induces periostin through a β-catenin-independent mechanism.\",\n      \"evidence\": \"Wnt-3 viral infection, GSK-3 inhibition, and β-catenin overexpression/antisense in mouse mammary epithelial cells\",\n      \"pmids\": [\"10884377\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream effectors of the non-canonical Wnt branch driving POSTN remain unidentified\", \"Not tested in mesenchymal cell types where periostin is most abundant\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Mapping periostin expression to developing cardiac cushions and trabeculae, with induction by TGF-β and BMP, established it as an integrin-binding matricellular factor in heart morphogenesis.\",\n      \"evidence\": \"In situ hybridization and Northern analysis in chick cardiac development\",\n      \"pmids\": [\"15532025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No loss-of-function data at this stage\", \"Specific integrin partners in cardiac tissue not identified\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrating that both TGF-β1 and mechanical strain converge on FAK to induce periostin expression answered how mechanical loading is transduced to matrix remodeling gene programs.\",\n      \"evidence\": \"Cyclic strain on PDL fibroblasts with FAK inhibition and FAK-null fibroblasts\",\n      \"pmids\": [\"20940356\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"FAK-dependent transcription factor mediating POSTN induction not identified\", \"Tested only in periodontal ligament fibroblasts\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showing that periostin promotes lymphangiogenesis via Src/Akt activation and VEGF-C upregulation extended its functional repertoire beyond matrix adhesion to vascular remodeling in tumors.\",\n      \"evidence\": \"Conditioned media tube formation assays with kinase inhibitors and xenograft correlation in HNSCC\",\n      \"pmids\": [\"22952986\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Receptor on lymphatic endothelial cells not defined\", \"No genetic loss-of-function in vivo\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Multiple studies defined the specific integrin–effector cascades through which periostin acts: α6β4/JNK suppresses PPARα in hepatocytes causing steatosis; integrins/FAK/PI3K/AKT/ERK drive valvulogenesis; and periostin on dendritic cells is required for maximal allergic airway inflammation.\",\n      \"evidence\": \"KO mice, neutralizing antibodies, integrin blockade, explant cultures in liver, heart, and airway models; DC adoptive transfer restoring allergic responses in Postn−/− mice\",\n      \"pmids\": [\"25003192\", \"24469446\", \"24996263\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How periostin selectively engages different integrin heterodimers in different tissues is unknown\", \"Structural basis for integrin selectivity not resolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Periostin was shown to sustain myofibroblast persistence via ROCK-dependent proliferation and α-SMA maintenance, and its expression under compressive force was confirmed to require TGF-β1 signaling, linking mechanical loading to fibrotic matrix remodeling.\",\n      \"evidence\": \"3D collagen contraction with ROCK inhibitor in scar fibroblasts; compressive force apparatus with TGF-β1 inhibitor/neutralizing antibody in PDL fibroblasts; Schwann cell migration assays in Postn-KO DRG explants\",\n      \"pmids\": [\"25421393\", \"25870205\", \"26187852\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ROCK activation is integrin-dependent not tested directly\", \"Periostin's role in nerve repair beyond Schwann cell migration not explored\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrating that fibrocyte-secreted periostin drives myofibroblast differentiation via β1-integrin and upregulates CTGF and LOX established periostin as a paracrine amplifier of pulmonary fibrosis.\",\n      \"evidence\": \"Adoptive transfer of WT vs Postn−/− fibrocytes in bleomycin model with in vitro receptor identification\",\n      \"pmids\": [\"27435108\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream signaling from β1-integrin to CTGF/LOX transcription not dissected\", \"Relevance to human IPF fibrosis not directly demonstrated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A burst of studies in 2020 extended periostin signaling to new receptors (DDR1 in chondrocytes), new effectors (NF-κB/ADAMTS5 in cartilage resorption, integrin-β1/RhoA in palatal wound healing), renal protection (integrin-β1 on tubular cells inhibiting apoptosis and promoting macrophage proliferation), and tumor immunosuppression (αvβ3/PI3K/AKT/NF-κB recruiting immunosuppressive microglia in glioblastoma).\",\n      \"evidence\": \"DDR1-KO chondrocytes and pharmacological inhibition; NF-κB inhibitor rescue; Postn−/− palatal wound model; conditional tubule-specific overexpression and Postn-KO in renal IRI; POSTN-depleted GSCs with ChIP-seq, tumorsphere assays, and orthotopic xenografts\",\n      \"pmids\": [\"32330138\", \"31840212\", \"32777343\", \"31690575\", \"39227950\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"DDR1 as a periostin receptor has not been confirmed by direct binding assay\", \"Whether NF-κB activation in tumors versus cartilage uses the same receptor is unknown\", \"Relative contribution of autocrine versus paracrine periostin in GBM niche not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Discovery of a HIF-1α–periostin positive feedback loop via TrkB in pulmonary hypertension revealed how periostin self-amplifies its own expression in hypoxic vascular disease, also linking to ET-1 and VEGF production.\",\n      \"evidence\": \"siRNA knockdown epistasis of HIF-1α, POSTN, and TrkB in hPAECs; Sugen/hypoxia and chronic hypoxia mouse PH models\",\n      \"pmids\": [\"32752980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction between periostin and TrkB not demonstrated\", \"Whether this feedback loop operates in other hypoxic tissues is untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identification of FAM20C as a direct kinase that phosphorylates periostin Fasciclin I domains provided the first post-translational modification mechanism, showing that the interaction is kinase-activity-independent for binding but required for phosphorylation.\",\n      \"evidence\": \"In vitro kinase assay with WT and kinase-dead D478A FAM20C, domain mapping pulldown, co-localization in PDL ECM\",\n      \"pmids\": [\"33051588\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphorylation sites on periostin not mapped\", \"Functional consequence of FAM20C-mediated phosphorylation on periostin activity unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrating that a short periostin isoform (lacking exon 17) on exosome surfaces—but not full-length periostin—drives cardiomyocyte cell-cycle re-entry via FAK/YAP established the first clear isoform-specific function.\",\n      \"evidence\": \"Cryo-EM immune-gold labeling, isoform-specific antibodies, FAK inhibitor, YAP siRNA, neonatal rat and human iPSC-derived cardiomyocytes in vitro and in vivo post-MI\",\n      \"pmids\": [\"33897872\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which exon 17 deletion alters integrin engagement or FAK activation is unknown\", \"Whether this isoform is generated by regulated alternative splicing or constitutive remains unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Periostin was linked to metabolic regulation via TGF-β/Smad-induced NAP1L2 upregulation, which recruits SIRT3 to deacetylate H3K27ac at BCAA catabolism gene promoters, connecting periostin to diabetic cardiomyopathy through impaired branched-chain amino acid metabolism.\",\n      \"evidence\": \"RNA-seq, ChIP for H3K27ac, gain/loss-of-function in diabetic mice and cardiac fibroblasts, TGF-β pathway inhibition\",\n      \"pmids\": [\"37993768\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether periostin-NAP1L2 axis operates outside the diabetic heart is untested\", \"Direct paracrine effect of fibroblast-derived periostin on cardiomyocyte BCAA metabolism not shown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Conditional deletion of PIEZO1 in periostin-expressing myofibroblasts revealed that mechanosensation through PIEZO1 is required for YAP/TAZ nuclear localization and sustained fibrotic activation, with Yap/Taz deletion fully phenocopying PIEZO1 loss, placing PIEZO1 upstream of YAP/TAZ in periostin-lineage cells.\",\n      \"evidence\": \"Postn-CreERT2 lineage tracing, conditional Piezo1 KO and Yap/Taz double KO in Postn+ cells, bleomycin fibrosis model\",\n      \"pmids\": [\"40454481\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether PIEZO1 signals through integrins or independently of periostin-integrin axis is unresolved\", \"Applicability to non-pulmonary fibrotic organs not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: the structural basis for isoform-specific and tissue-specific integrin engagement; the identity and functional consequences of FAM20C phosphorylation sites; and how periostin coordinates its distinct roles in fibrosis, immunity, and tumor immunosuppression at the single-cell level.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystal structure of periostin bound to any integrin\", \"Phosphosite mapping and functional phosphomutant studies lacking\", \"Single-cell resolution of periostin paracrine circuits not yet achieved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [1, 2, 22]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [0, 1, 4, 20]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 7, 8, 25]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [8, 12, 22]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 3, 4, 20]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1, 4, 5, 11, 20]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [3, 8, 17, 24]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 16, 22]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [20, 23]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 4, 13, 18]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ITGB1\",\n      \"ITGAV\",\n      \"ITGB3\",\n      \"ITGA6\",\n      \"ITGB4\",\n      \"FAM20C\",\n      \"DDR1\",\n      \"YAP1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}