Affinage

TGFBI

Transforming growth factor-beta-induced protein ig-h3 · UniProt Q15582

Length
683 aa
Mass
74.7 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TGFBI encodes a secreted extracellular matrix protein (TGFBIp/βig-h3) that functions as a multivalent integrin ligand and collagen-binding matricellular factor, regulating cell adhesion, migration, survival, and tissue remodeling across diverse biological contexts. TGFBIp engages multiple integrins—including αvβ3, αvβ5, α3β1, and αMβ2—through cooperative action of its four FAS1 domains and a C-terminal RGD motif, achieving high-affinity binding (Kd ~38 nM for αvβ3) that underlies its anti-angiogenic, pro-metastatic, and microtubule-stabilizing activities depending on cellular context (PMID:23792174, PMID:18245446, PMID:18068629, PMID:30048528). Downstream of integrin engagement, TGFBIp activates FAK, Src, PI3K/Akt/mTOR, Rho GTPase, and Stat3 signaling cascades to control cell survival, proliferation, and drug sensitivity, while also binding Notch-1 to regulate adipocyte browning and interacting with periostin via EMI domains prior to secretion (PMID:24728038, PMID:35673564, PMID:36854775, PMID:19478074). Missense mutations in TGFBI (e.g., R124H, R124C) cause corneal dystrophies by impairing periostin interaction, mislocalizing TGFBIp to lysosomes, and disrupting autophagic clearance through defective autophagosome–lysosome fusion (PMID:19478074, PMID:22995918, PMID:12824240). Transcriptionally, TGFBI is regulated by TGFβ/Smad3 signaling and HIF-2α under hypoxia, and its protein stability is controlled by OTUB1-mediated deubiquitination at K22/K25 (PMID:21310903, PMID:38365849, PMID:36994729).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Establishing that corneal dystrophy mutations in TGFBI are not merely loss-of-function but actively toxic: overexpression of R124C and R555W mutants induces caspase-3-dependent apoptosis through the C-terminal PDI motif, identifying a specific integrin-binding site as the effector domain for mutant cytotoxicity.

    Evidence Transfection of mutant BIGH3-EGFP constructs with truncation/site-directed mutagenesis of PDI domain, caspase-3 activation in corneal and HeLa cells

    PMID:12824240

    Open questions at the time
    • Whether endogenous mutant protein levels are sufficient to trigger apoptosis in vivo
    • Whether PDI-mediated apoptosis is specific to corneal cell types or universal
  2. 2007 High

    Resolving how an ECM protein controls drug sensitivity: TGFBIp stabilizes microtubules through integrin-dependent FAK-Rho signaling, and its loss confers specific paclitaxel resistance in ovarian cancer, establishing TGFBIp as a functional link between extracellular matrix and cytoskeletal drug targets.

    Evidence TGFBI-deficient ovarian cancer cells rescued with recombinant protein; FAK/Rho inhibition and microtubule stabilization assays

    PMID:18068629

    Open questions at the time
    • Whether TGFBIp-mediated microtubule stabilization operates through direct tubulin interaction or solely through integrin signaling
    • Generalizability to other microtubule-targeting agents
  3. 2008 High

    Defining TGFBIp's pro-metastatic mechanism: TGFBIp promotes cancer cell extravasation by disrupting endothelial VE-cadherin junctions via integrin αvβ5-Src signaling, identifying a paracrine ECM-to-endothelium axis in metastasis.

    Evidence Ectopic expression and shRNA knockdown in in vivo colon cancer metastasis models with integrin αvβ5-Src pathway delineation

    PMID:18245446

    Open questions at the time
    • Whether endothelial cells or tumor cells are the primary source of TGFBIp in metastasis
    • Structural basis of αvβ5 selectivity over other integrins in this context
  4. 2009 High

    Identifying TGFBIp's pre-secretory partner and the molecular basis of corneal dystrophy protein mislocalization: TGFBIp interacts with periostin via EMI domains in the trans-Golgi network, and the R124H dystrophy mutation disrupts this interaction, causing aberrant redistribution to lysosomes.

    Evidence Reciprocal Co-IP, domain mapping with EMI constructs, confocal colocalization in patient-derived corneal fibroblasts

    PMID:19478074

    Open questions at the time
    • Whether periostin interaction is required for normal TGFBIp secretion or only quality control
    • Whether other dystrophy mutations similarly disrupt periostin binding
  5. 2011 Medium

    Establishing how TGFBIp signals intracellularly and how its transcription is controlled: TGFBIp suppresses mesothelioma via PI3K/Akt/mTOR signaling, and TGFβ/Smad3 signaling drives TGFBI transcription, with GSK-3β modulating Smad3 activity.

    Evidence shRNA knockdown/overexpression with signaling readouts in mesothelioma; Co-IP of GSK-3β–Smad3, LiCl treatment in GCD2 fibroblasts

    PMID:21310903 PMID:21701776

    Open questions at the time
    • Which integrin mediates PI3K/Akt/mTOR activation in mesothelioma
    • Direct Smad3 binding to TGFBI promoter not confirmed by ChIP in these studies
  6. 2012 High

    Revealing the proteostasis mechanism for mutant TGFBIp clearance: GCD2-mutant TGFBIp is degraded by autophagy rather than the proteasome, and the R124H mutation impairs autophagosome–lysosome fusion, causing accumulation of uncleared mutant protein—providing a mechanistic basis for corneal deposits.

    Evidence Autophagy flux assays with bafilomycin A1, LC3-II/SQSTM1 analysis, rapamycin rescue in primary GCD2 corneal fibroblasts

    PMID:22995918

    Open questions at the time
    • Whether the fusion defect is specific to TGFBIp-containing autophagosomes or represents a general autophagy impairment
    • Identity of the autophagy receptor for TGFBIp
  7. 2013 High

    Quantifying the multi-domain integrin-binding mechanism: all four FAS1 domains plus the RGD motif cooperate to achieve ~2300-fold higher affinity for αvβ3 than a single FAS1 domain alone (Kd ~38 nM), explaining TGFBIp's potent biological activities.

    Evidence Quantitative binding assays with recombinant domain constructs, in vitro anti-angiogenesis and in vivo tumor targeting

    PMID:23792174

    Open questions at the time
    • No crystal structure of the TGFBIp–integrin complex
    • Whether domain cooperativity differs across integrin subtypes
  8. 2014 Medium

    Extending TGFBIp's physiological roles beyond the cornea: Tgfbi-null mice show cartilage degradation with elevated MMP13, and TGFBIp activates FAK/AKT/mTOR in pancreatic islets to promote survival, establishing TGFBIp as a systemic matrix factor for tissue homeostasis.

    Evidence Tgfbi KO mice with skeletal phenotyping; phosphoprotein arrays and siRNA pathway validation in KO islets

    PMID:24728038 PMID:25450762

    Open questions at the time
    • Whether cartilage phenotype is integrin-dependent
    • Human relevance of islet survival function
  9. 2017 High

    Establishing transcriptional control of TGFBI by AR-SPDEF axis in prostate cancer: androgen signaling through SPDEF represses TGFBI, and androgen deprivation therapy elevates TGFBIp to promote EMT and bone/brain metastasis, revealing an iatrogenic pro-metastatic mechanism.

    Evidence SPDEF KD/OE epistasis, xenograft bone/brain metastasis models, patient tissue before/after ADT

    PMID:28811384

    Open questions at the time
    • Which integrin mediates TGFBI's metastatic function in prostate cancer
    • Whether TGFBI inhibition could mitigate ADT-induced metastasis
  10. 2021 High

    Identifying post-translational stabilization of TGFBIp: OTUB1 deubiquitinates TGFBIp at K22 and K25 in a catalytic-independent manner, stabilizing the protein and promoting glycolysis-driven angiogenesis in infantile hemangioma.

    Evidence Mass spectrometry, Co-IP, ubiquitination assays with K22/K25 mutants, OTUB1 KD/OE, in vivo hemangioma model

    PMID:36994729

    Open questions at the time
    • E3 ligase responsible for TGFBIp ubiquitination at K22/K25 not identified
    • How intracellular ubiquitination regulates a secreted protein's stability
  11. 2022 Medium

    Defining TGFBIp's role in glioblastoma stem cell maintenance: TGFBIp activates an integrin αvβ5-Src-Stat3 signaling axis in glioblastoma stem cells, promoting self-renewal and tumor growth in orthotopic models.

    Evidence Recombinant TGFBIp treatment with pathway inhibition, orthotopic xenografts, Western blot/ELISA

    PMID:35673564

    Open questions at the time
    • Whether TGFBIp is tumor- or stroma-derived in glioblastoma
    • Whether Stat3 activation is direct or secondary to Src
  12. 2023 Medium

    Revealing a non-integrin receptor for TGFBIp: TGFBIp directly binds Notch-1 to activate Notch signaling in adipocytes, controlling adipsin secretion and adipocyte browning, establishing a metabolic role for this ECM protein.

    Evidence Co-immunoprecipitation of TGFBIp–Notch-1, Tgfbi KO mice on high-fat diet, adipocyte browning assays

    PMID:36854775

    Open questions at the time
    • Binding interface between TGFBIp and Notch-1 not mapped
    • Whether Notch activation is ligand-mimetic or modulatory
  13. 2024 Medium

    Establishing direct transcriptional regulation by HIF-2α: HIF-2α binds the TGFBI promoter under hypoxia to upregulate expression, and TGFBIp promotes cisplatin resistance via PI3K/Akt-dependent enhancement of DNA damage repair.

    Evidence ChIP/promoter binding assay for HIF-2α, TGFBI siRNA KD with DNA repair marker analysis in cisplatin-resistant ovarian cancer cells

    PMID:38365849

    Open questions at the time
    • Whether HIF-2α regulation is conserved across tumor types
    • Direct mechanism linking extracellular TGFBIp to nuclear DNA repair machinery

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive functional characterization, no structural model of the full-length TGFBIp–integrin complex exists, the E3 ubiquitin ligase targeting TGFBIp is unknown, the autophagy receptor for TGFBIp clearance has not been identified, and the mechanism by which an extracellular/secreted protein activates nuclear DNA repair pathways remains unexplained.
  • No full-length TGFBIp–integrin co-crystal structure
  • E3 ligase for K22/K25 ubiquitination unidentified
  • Autophagy receptor mediating TGFBIp degradation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 4 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1500931 Cell-Cell communication 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
DKK3ITGAMITGAVITGB3ITGB5NOTCH1OTUB1POSTN

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 TGFBI (betaig-h3) promotes cancer cell extravasation by inducing dissociation of VE-cadherin junctions between endothelial cells via activation of the integrin αvβ5-Src signaling pathway, promoting colon cancer metastasis. Ectopic expression and shRNA knockdown in vivo metastasis models; mechanistic pathway delineation via integrin αvβ5-Src signaling Genes & development High 18245446
2007 Loss of TGFBI causes specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells; recombinant TGFBI restores paclitaxel sensitivity through integrin-dependent FAK- and Rho-dependent stabilization of microtubules. Loss-of-function (TGFBI-deficient cells), rescue with recombinant TGFBI protein, FAK/Rho pathway inhibition assays, in vitro microtubule stabilization assay Cancer cell High 18068629
2009 TGFBI interacts with periostin via their N-terminal EMI domains; both proteins colocalize in the trans-Golgi network and associate prior to secretion. The corneal dystrophy-associated R124H mutation severely impairs TGFBI-periostin interaction and causes aberrant redistribution of mutant TGFBI to lysosomes. Co-immunoprecipitation, domain mapping (EMI domain constructs), confocal colocalization, subcellular fractionation, patient-derived corneal fibroblasts The Journal of biological chemistry High 19478074
2012 Mutant TGFBI (R124H; GCD2) is degraded by autophagy but not the ubiquitin/proteasome pathway; GCD2 corneal fibroblasts display defective autophagosome-lysosome fusion leading to impaired clearance of mutant TGFBIp and accumulation of autophagosomes containing mutant protein. Autophagy flux assays (bafilomycin A1 treatment), LC3-II/SQSTM1 western blot, confocal colocalization, rapamycin rescue experiments, caspase-3 activation assays in primary patient corneal fibroblasts Autophagy High 22995918
2003 Overexpression of mutant TGFBI (R124C, R555W, and others) induces apoptosis in corneal and HeLa cells through caspase-3 activation; apoptosis requires the C-terminal domain and specifically the PDI site (Pro-Asp-Ile, residues 616-618), a known site of interaction with α3β1 integrins. Transfection of mutant BIGH3-EGFP constructs, Hoechst/propidium iodide and annexin V staining, caspase-3 activation assay, truncation and site-specific mutagenesis of the PDI domain Investigative ophthalmology & visual science High 12824240
2013 TGFBI binds αvβ3 integrin with high affinity (Kd ~3.8×10⁻⁸ M) through cooperative action of all four FAS1 domains and the RGD motif; this multi-domain cooperation confers ~2300-fold higher affinity than a single FAS1 domain alone and underlies potent anti-angiogenic and anti-tumor activities. Binding affinity assay (Kd measurement), recombinant domain constructs, in vitro anti-angiogenesis assays, in vivo tumor targeting experiments Biochimica et biophysica acta High 23792174
2011 TGFBI suppresses mesothelioma progression via the PI3K/Akt/mTOR signaling pathway; loss of TGFBI elevates c-myc/cyclin D1/phospho-Rb and activates PI3K/Akt/mTOR signaling, while ectopic TGFBI expression reverses these changes. shRNA knockdown and ectopic overexpression, western blot for signaling pathway components, clonogenic and soft-agar growth assays International journal of oncology Medium 21701776
2011 Lithium (LiCl) reduces TGFBI expression by decreasing pSmad3 levels and enhancing interaction between GSK-3β and Smad3, and by inducing autophagy (elevated LC3-II/I ratio), thereby reducing normal and mutant TGFBIp accumulation in GCD2 corneal fibroblasts. Western blot (pSmad3, pGSK-3α/β, LC3-II), RT-PCR, co-immunoprecipitation of GSK-3β and Smad3, dose-response assays in primary corneal fibroblasts Investigative ophthalmology & visual science Medium 21310903
2011 Corneal deposits in GCD2 (R124H mutation) specifically accumulate TGFBIp along with serum amyloid P-component, clusterin, and type III collagen. In LCD amyloid (V624M), a C-terminal fragment of TGFBIp (residues Y571-R588 from FAS1-4 domain) accumulates with serine protease HtrA1, which shows proteolytic cleavage sites in FAS1-4, suggesting HtrA1 mediates proteolytic processing of amyloidogenic TGFBIp. Laser capture microdissection, tandem mass spectrometry, label-free quantitative proteomics of corneal deposits Experimental eye research Medium 22155582
2017 AR signaling stimulates SPDEF transcription factor activity, which represses TGFBI expression; androgen deprivation therapy (ADT) reduces nuclear SPDEF and increases TGFBI, and TGFBI promotes EMT and bone/brain metastasis of prostate cancer. TGFBI was identified as a type 1, 2, and 4 collagen-binding protein mediating this effect. KD/OE in prostate cancer cell lines, xenograft mouse models (bone/brain metastasis), patient tissue before/after ADT, SPDEF overexpression/knockdown Science signaling High 28811384
2014 TGFBI activates the FAK/AKT/AKT1S1/RPS6/EIF4EBP1 signaling pathway in islets to promote cell survival and function; phosphoprotein array and siRNA knockdown of pathway components confirmed mechanistic relevance. Phosphoprotein array analysis in TGFBI KO islets, recombinant TGFBI stimulation, AKT chemical inhibitor, siRNA knockdown of AKT1S1/RPS6/EIF4EBP1, islet survival/function assays Human molecular genetics Medium 24728038
2009 In zebrafish embryos, TGFBI localizes to myosepta (myotendinous junctions) and is required for myofibril bundling and muscle fibre growth; morpholino knockdown causes reduced fibre growth and disrupted myofibril bundles without affecting fibre attachment to myosepta. GFP-tagged TGFBI live imaging, antisense morpholino knockdown, muscle fibre phenotypic analysis in zebrafish embryos Developmental dynamics Medium 19097068
2014 Tgfbi deficiency in mice leads to reduced skeletal size and cartilage matrix degradation, with increased MMP13 and decreased type II collagen in articular cartilage, indicating TGFBI is required for maintaining cartilage matrix homeostasis. Tgfbi knockout mice, skeletal preparation, safranin O/trichrome staining, IHC for type II collagen and MMP13 Calcified tissue international Medium 25450762
2021 TGFBI promotes tumor angiogenesis in colorectal cancer metastasis; non-canonical TGFβ signaling positively regulates TGFBI expression, and TGFBI inhibition reduces liver metastasis in vivo. TGFBI knockdown, in vivo orthotopic CRC liver metastasis model, TGFβ pathway inhibition, radiolabeled antibody targeting in vivo Theranostics Medium 33408771
2022 TGFBI promotes glioblastoma stem cell maintenance and tumor growth through integrin αvβ5-Src-Stat3 signaling; recombinant TGFBI activates this pathway in GSCs in vitro and in orthotopic xenografts. Recombinant TGFBI treatment, integrin αvβ5-Src-Stat3 pathway inhibition, orthotopic xenograft models, Western blot, ELISA Theranostics Medium 35673564
2013 TGFBI inhibits CXCL12-induced migration of hematopoietic stem/progenitor cells (HSPCs) over fibronectin by inhibiting PMA-induced RAC1 activation and ERK phosphorylation, without altering integrin expression or actin polymerization. BIGH3 overexpression in primary HSPCs and HL60 cells, adhesion and ECIS assays, migration assays, RAC1 GTPase activity assay, ERK phosphorylation western blot Cell adhesion & migration Medium 24152593
2019 TGFBI secreted by MSCs (present in both soluble and extracellular vesicle forms) acts as a chondroprotective factor; TGFBI silencing in MSCs abolishes their inductive effect on chondrocyte anabolic markers, and injection of TGFBI-silenced MSCs fails to protect mice from OA development. siRNA silencing, co-culture assays, in vivo OA mouse model, extracellular vesicle fractionation and TGFBI detection Biomaterials Medium 31648137
2024 Cathepsin D (Cat D) targets TGFBI to regulate macrophage polarization; Cat D KO elevates TGFBI expression in cancer cells, which reduces M2-like TAM polarization through CCL20 chemokine secretion. Double Cat D/TGFBI KO rescues the inhibitory effects of Cat D KO on metastasis. Cat D KO and TGFBI KO cancer cells, double KO rescue experiments, RNA-seq, secretome analysis, in vivo tumor metastasis models Experimental & molecular medicine Medium 38297161
2023 TGFBI binds Notch-1 and stimulates its activation in adipocytes; TGFBI deficiency suppresses adipsin secretion via Notch-1-dependent signaling, leading to adipocyte browning and protection against obesity-induced metabolic dysfunction. TGFBI KO mice, co-immunoprecipitation of TGFBI and Notch-1, adipocyte browning assays, high-fat diet model Experimental & molecular medicine Medium 36854775
2021 TGFBI promotes angiogenesis in infantile hemangioma through OTUB1-mediated deubiquitination; OTUB1 interacts with TGFBI and deubiquitinates it at K22 and K25 residues in a catalytic-independent manner, stabilizing TGFBI and thereby promoting glycolysis-driven angiogenesis. Mass spectrometry, Co-IP, half-life assay, ubiquitination assay with site-specific mutants (K22, K25), OTUB1 KD/OE, in vitro angiogenesis assays, in vivo IH model Arteriosclerosis, thrombosis, and vascular biology High 36994729
2021 Deletion of Tgfbi in MMTV-PyMT mammary tumor model dramatically reduces cancer stem cell (CSC) content and lung metastasis by normalizing tumor vasculature, improving perfusion, and decreasing tumor hypoxia. MMTV-PyMT × TgfbiΔ/Δ mouse cross, RNAseq, IHC and FACS of vasculature and immune compartment, bone marrow transplantation for source identification Molecular oncology Medium 33080107
2022 DKK3 interacts extracellularly with TGFBI; this interaction inhibits DKK3's functions supporting cell adhesion, motility, and invasion through focal adhesion kinase signaling in hepatocellular carcinoma cells. Co-immunoprecipitation of secreted DKK3 and TGFBI, cell adhesion/motility/invasion assays, FAK signaling readout in HCC and HEK293 cells The FEBS journal Medium 35574828
2018 TGFBI mediates cytokine-activated eosinophil adhesion via αMβ2 integrin; eosinophils on TGFBI substrate adopt distinct morphologies (acorn vs. pancake) depending on protein coating concentration, regulating their migratory behavior. Eosinophil adhesion and motility assays on TGFBI-coated substrates, αMβ2 blocking antibodies, video microscopy of cell morphology PloS one Medium 30048528
2016 TGFβ induces BIGH3 expression in retinal pericytes and endothelial cells; BIGH3 protein acts in an autocrine loop to induce retinal pericyte apoptosis in a dose-dependent manner. Blocking antibodies against BIGH3 inhibit TGFβ-induced apoptosis. TUNEL assay, qPCR for BIGH3 mRNA, western blot, recombinant BIGH3 dose-response, neutralizing antibody inhibition, IHC in human post-mortem diabetic retina Eye (London, England) Medium 27564721
2013 TGFBI regulates melanoma cell proliferation through cyclins and cyclin-dependent kinases; TGFBI silencing increases melanoma cell motility/invasion but drastically reduces proliferation, identifying a role for TGFBI in cell cycle progression rather than dissemination. shRNA silencing, in vivo lung metastasis model (tail vein injection), cell cycle analysis, cyclin/CDK western blot The Journal of investigative dermatology Medium 24499734
2017 Proteomic profiling of TGFBI-null mouse corneas shows that TGFBIp interacts with type VI and XII collagens (among others); POSTN cannot compensate for loss of TGFBIp; and TGFBI mRNA is restricted to corneal epithelial cells. Quantitative proteomics of TGFBI-/- vs wild-type corneas, in situ hybridization for TGFBI mRNA, histology The FEBS journal Medium 29117645
2024 HIF-2α (but not HIF-1α) directly binds to the TGFBI promoter under hypoxia to upregulate TGFBI transcription; TGFBI promotes cisplatin resistance in ovarian cancer by activating PI3K/Akt pathway to reduce apoptosis and enhance DNA damage repair (upregulating p-p95/NBS1, RAD51, p-DNA-PKcs, DNA Ligase IV, Artemis, BCL2). HIF-1α/HIF-2α plasmid transfection, ChIP/promoter binding assay, TGFBI siRNA KD, western blot for DNA repair and apoptosis markers, PI3K/Akt pathway analysis in cisplatin-resistant cells Scientific reports Medium 38365849

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI. The FEBS journal 267 24988946
2008 Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes & development 193 18245446
2007 The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel. Cancer cell 187 18068629
2012 Transforming growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): a matrix protein with dual functions in ovarian cancer. International journal of molecular sciences 110 22949874
2020 Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C. Cell death & disease 107 32312959
2000 LCD1: an essential gene involved in checkpoint control and regulation of the MEC1 signalling pathway in Saccharomyces cerevisiae. The EMBO journal 107 11060031
2022 TGFBI secreted by tumor-associated macrophages promotes glioblastoma stem cell-driven tumor growth via integrin αvβ5-Src-Stat3 signaling. Theranostics 93 35673564
2015 Pathogenesis and treatments of TGFBI corneal dystrophies. Progress in retinal and eye research 92 26612778
2001 Survey of patients with granular, lattice, avellino, and Reis-Bücklers corneal dystrophies for mutations in the BIGH3 and gelsolin genes. Archives of ophthalmology (Chicago, Ill. : 1960) 78 11146721
2021 The role of the extracellular matrix protein TGFBI in cancer. Cellular signalling 74 33940163
2019 TGFBI secreted by mesenchymal stromal cells ameliorates osteoarthritis and is detected in extracellular vesicles. Biomaterials 70 31648137
2014 Clinical and genetic aspects of the TGFBI-associated corneal dystrophies. The ocular surface 64 25284770
1999 Heterogeneity in granular corneal dystrophy: identification of three causative mutations in the TGFBI (BIGH3) gene-lessons for corneal amyloidogenesis. Human mutation 63 10425035
1999 A novel mutation at codon 124 (R124L) in the BIGH3 gene is associated with a superficial variant of granular corneal dystrophy. Archives of ophthalmology (Chicago, Ill. : 1960) 61 9930165
2005 TGFBI gene mutations causing lattice and granular corneal dystrophies in Indian patients. Investigative ophthalmology & visual science 60 15623763
2004 Two mutations in the TGFBI (BIGH3) gene associated with lattice corneal dystrophy in an extensively studied family. Investigative ophthalmology & visual science 60 15111592
2006 A subset of patients with epithelial basement membrane corneal dystrophy have mutations in TGFBI/BIGH3. Human mutation 58 16652336
2021 Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis. Theranostics 56 33408771
2009 Corneal dystrophy-associated R124H mutation disrupts TGFBI interaction with Periostin and causes mislocalization to the lysosome. The Journal of biological chemistry 56 19478074
2023 A novel role of TGFBI in macrophage polarization and macrophage-induced pancreatic cancer growth and therapeutic resistance. Cancer letters 55 37865162
2012 Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy type 2. Autophagy 54 22995918
2000 Genomic characterization and embryonic expression of the mouse Bigh3 (Tgfbi) gene. Biochemical and biophysical research communications 54 10913330
1999 Chitin synthase III: synthetic lethal mutants and "stress related" chitin synthesis that bypasses the CSD3/CHS6 localization pathway. Proceedings of the National Academy of Sciences of the United States of America 54 10500155
2019 Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer. Breast cancer research : BCR 52 31277676
2017 Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. Science signaling 52 28811384
2018 Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1. Oncogene 51 29858602
2015 The role of TGFBI (βig-H3) in gastrointestinal tract tumorigenesis. Molecular cancer 49 25889002
2011 Composition and proteolytic processing of corneal deposits associated with mutations in the TGFBI gene. Experimental eye research 49 22155582
2021 MiR-21-5p Induces Pyroptosis in Colorectal Cancer via TGFBI. Frontiers in oncology 48 33614494
2020 Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies. Progress in retinal and eye research 47 32004730
2018 Enhanced Expression of TGFBI Promotes the Proliferation and Migration of Glioma Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 47 30196284
2012 TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel-Lindau tumor suppressor. Urology 47 22341602
2010 Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature. Molecular vision 46 20664689
2012 The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression. BMC cancer 45 22695319
2002 Clinical outcome of eight BIGH3-linked corneal dystrophies. Ophthalmology 45 11927442
2020 TGFBI modulates tumour hypoxia and promotes breast cancer metastasis. Molecular oncology 43 33080107
2013 Multiple FAS1 domains and the RGD motif of TGFBI act cooperatively to bind αvβ3 integrin, leading to anti-angiogenic and anti-tumor effects. Biochimica et biophysica acta 43 23792174
2010 Frequent promoter hypermethylation of TGFBI in epithelial ovarian cancer. Gynecologic oncology 42 20421128
2001 BIGH3 gene mutations and rapid detection in Korean patients with corneal dystrophy. Cornea 42 11685063
1999 Varied appearance of cornea of patients with corneal dystrophy associated with R124H mutation in the BIGH3 gene. Cornea 41 10422854
2014 TGF-β-induced (TGFBI) protein in melanoma: a signature of high metastatic potential. The Journal of investigative dermatology 40 24499734
2006 Systemic investigation of keratoepithelin deposits in TGFBI/BIGH3-related corneal dystrophy. Molecular vision 39 16710170
2017 Repair of the TGFBI gene in human corneal keratocytes derived from a granular corneal dystrophy patient via CRISPR/Cas9-induced homology-directed repair. Scientific reports 38 29196743
2013 Oncostatin M promotes mesenchymal stem cell-stimulated tumor growth through a paracrine mechanism involving periostin and TGFBI. The international journal of biochemistry & cell biology 38 23735324
2004 Polymorphic corneal amyloidosis: a disorder due to a novel mutation in the transforming growth factor beta-induced (BIGH3) gene. Ophthalmology 38 15177960
2003 Induction of apoptosis in human corneal and HeLa cells by mutated BIGH3. Investigative ophthalmology & visual science 38 12824240
2018 miR-21-5p induces cell proliferation by targeting TGFBI in non-small cell lung cancer cells. Experimental and therapeutic medicine 37 30542417
2018 Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma. Journal of neuro-oncology 36 29294230
2000 Immunohistology of kerato-epithelin in corneal stromal dystrophies associated with R124 mutations of the BIGH3 gene. Current eye research 35 11262611
2014 Development of allele-specific gene-silencing siRNAs for TGFBI Arg124Cys in lattice corneal dystrophy type I. Investigative ophthalmology & visual science 33 24425855
2011 Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway. International journal of oncology 33 21701776
2011 Inhibition of TGFBIp expression by lithium: implications for TGFBI-linked corneal dystrophy therapy. Investigative ophthalmology & visual science 32 21310903
1998 The classic form of granular corneal dystrophy associated with R555W mutation in the BIGH3 gene is rare in Japanese patients. American journal of ophthalmology 32 9744382
2019 Mutation update: TGFBI pathogenic and likely pathogenic variants in corneal dystrophies. Human mutation 30 30830990
2019 Evaluation of TGFBI corneal dystrophy and molecular diagnostic testing. Eye (London, England) 29 30760895
2014 TGFBI (βIG-H3) is a diabetes-risk gene based on mouse and human genetic studies. Human molecular genetics 29 24728038
2003 The lower cell density of leaf parenchyma in the Arabidopsis thaliana mutant lcd1-1 is associated with increased sensitivity to ozone and virulent Pseudomonas syringae. The Plant journal : for cell and molecular biology 29 12848826
2024 Cathepsin D promotes polarization of tumor-associated macrophages and metastasis through TGFBI-CCL20 signaling. Experimental & molecular medicine 28 38297161
2005 Novel mutation (V505D) of the TGFBI gene found in a Chinese family with lattice corneal dystrophy, type I. Japanese journal of ophthalmology 28 15838722
2003 Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty. Ophthalmology 28 12799235
2023 TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway. Experimental & molecular medicine 27 36854775
2017 Proteomic profiling of TGFBI-null mouse corneas reveals only minor changes in matrix composition supportive of TGFBI knockdown as therapy against TGFBI-linked corneal dystrophies. The FEBS journal 26 29117645
1994 Assignment of granular corneal dystrophy Groenouw type I (CDGG1) to chromosome 5q. European journal of human genetics : EJHG 26 8044658
2009 The extracellular matrix protein TGFBI promotes myofibril bundling and muscle fibre growth in the zebrafish embryo. Developmental dynamics : an official publication of the American Association of Anatomists 25 19097068
2014 TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients. British journal of cancer 24 24481402
2014 Tgfbi deficiency leads to a reduction in skeletal size and degradation of the bone matrix. Calcified tissue international 24 25450762
2021 Torin 1 alleviates impairment of TFEB-mediated lysosomal biogenesis and autophagy in TGFBI (p.G623_H626del)-linked Thiel-Behnke corneal dystrophy. Autophagy 23 34403298
2021 Roles of a Cysteine Desulfhydrase LCD1 in Regulating Leaf Senescence in Tomato. International journal of molecular sciences 23 34884883
2020 Generation of mouse model of TGFBI-R124C corneal dystrophy using CRISPR/Cas9-mediated homology-directed repair. Scientific reports 23 32029872
2013 BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells. Cell adhesion & migration 23 24152593
2024 TGFBI: A novel therapeutic target for cancer. International immunopharmacology 22 38733822
2021 Endothelial angiogenic activity and adipose angiogenesis is controlled by extracellular matrix protein TGFBI. Scientific reports 22 33958649
2010 TGFBI mutation screening and genotype-phenotype correlation in north Indian patients with corneal dystrophies. Molecular vision 22 20680100
2021 Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis. Scientific reports 21 34686725
2016 TGFβ induces BIGH3 expression and human retinal pericyte apoptosis: a novel pathway of diabetic retinopathy. Eye (London, England) 21 27564721
2014 Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression. PloS one 21 25369402
2008 Overexpression of a mutant form of TGFBI/BIGH3 induces retinal degeneration in transgenic mice. Molecular vision 21 18568131
2022 Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway. Cellular oncology (Dordrecht, Netherlands) 20 35357655
2021 The LIN28B/TGF-β/TGFBI feedback loop promotes cell migration and tumour initiation potential in cholangiocarcinoma. Cancer gene therapy 20 34548635
2010 Detection of the most common corneal dystrophies caused by BIGH3 gene point mutations using a multispot gold-capped nanoparticle array chip. Analytical chemistry 20 20092310
2015 Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase. Acta crystallographica. Section D, Biological crystallography 19 25760614
2008 BIGH3 is overexpressed in clear cell renal cell carcinoma. Oncology reports 19 18357369
2008 A novel phenotype-genotype relationship with a TGFBI exon 14 mutation in a pedigree with a unique corneal dystrophy of Bowman's layer. Molecular vision 19 18728790
2017 BIGH3 Promotes Osteolytic Lesions in Renal Cell Carcinoma Bone Metastasis by Inhibiting Osteoblast Differentiation. Neoplasia (New York, N.Y.) 16 29190493
2015 Mutation Analysis of the TGFBI Gene in Consecutive Korean Patients With Corneal Dystrophies. Annals of laboratory medicine 15 25932442
2024 HIF-2α-dependent TGFBI promotes ovarian cancer chemoresistance by activating PI3K/Akt pathway to inhibit apoptosis and facilitate DNA repair process. Scientific reports 13 38365849
2023 FN1 and TGFBI are key biomarkers of macrophage immune injury in diabetic kidney disease. Medicine 13 37960829
2018 TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis. Stem cells and development 13 30084753
2015 BIGH3 protein and macrophages in retinal endothelial cell apoptosis. Apoptosis : an international journal on programmed cell death 13 25378215
2014 TGFBI, CHST6, and GSN gene analysis in Mexican patients with stromal corneal dystrophies. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 13 24801599
2002 An analysis of BIGH3 mutations in patients with corneal dystrophies in the Kyushu district of Japan. Japanese journal of ophthalmology 13 12225829
2022 Roles of DKK3 in cellular adhesion, motility, and invasion through extracellular interaction with TGFBI. The FEBS journal 12 35574828
2021 A novel variant in TGFBI causes keratoconus in a two-generation Chinese family. Ophthalmic genetics 12 34895010
2018 Control of cytokine-driven eosinophil migratory behavior by TGF-beta-induced protein (TGFBI) and periostin. PloS one 12 30048528
2016 Genetic analysis of CHST6 and TGFBI in Turkish patients with corneal dystrophies: Five novel variations in CHST6. Molecular vision 12 27829782
2013 A C-terminal fragment BIGH3 protein with an RGDRGD motif inhibits corneal neovascularization in vitro and in vivo. Experimental eye research 12 23562678
2011 Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade. Advances in experimental medicine and biology 12 21901626
2009 A novel mutation I522N within the TGFBI gene caused lattice corneal dystrophy I. Molecular vision 12 19956413
2023 OTUB1 Catalytic-Independently Deubiquitinates TGFBI and Mediates the Angiogenesis in Infantile Hemangioma by Regulating Glycolysis. Arteriosclerosis, thrombosis, and vascular biology 11 36994729
2022 MiR-766-3p Suppresses Malignant Behaviors and Stimulates Apoptosis of Colon Cancer Cells via Targeting TGFBI. Canadian journal of gastroenterology & hepatology 11 35083181