Affinage

TNC

Tenascin · UniProt P24821

Audit flag: ungrounded claim
Length
2201 aa
Mass
240.9 kDa
Annotated
2026-06-10
79 papers in source corpus 18 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Tenascin-C (TNC) is a secreted extracellular matrix glycoprotein that operates as a signaling scaffold to drive cell proliferation, migration, invasion, fibroblast activation, and tissue fibrosis across kidney, liver, muscle, and multiple cancers (PMID:39181396, PMID:41214839). Once deposited, TNC engages cell-surface receptors to activate downstream effector pathways: it triggers TLR4/NF-κB signaling to amplify pro-inflammatory and pro-fibrotic loops (upregulating CTGF and fibronectin) (PMID:33520106, PMID:41214839); it binds αv-containing integrins—notably αvβ1—to activate focal adhesion kinase (FAK) and promote tumor cell proliferation and invasion; it binds integrin α2 to activate TGF-β/Smad2/3 signaling in synovial fibroblasts (PMID:41660234); and it activates PI3K/AKT/mTOR signaling to enhance proliferation, survival, and migration (PMID:41427845, PMID:41980472). TNC further binds Wnt ligands and potentiates ligand-dependent Wnt signaling at the invasive tumor edge, and in muscle repair it is secreted by fibro-adipogenic progenitors and sensed by muscle stem cells through the surface receptor Annexin A2. TNC expression is tightly controlled at multiple levels: transcriptionally through factors including Twist1/Prrx1, CREB5, EN2 acting at a super-enhancer, and TBX5 (PMID:39181396, PMID:39915455, PMID:37987507, PMID:41660234); epigenetically through TDG-mediated DNA demethylation at the TNC locus (PMID:39090080); post-transcriptionally through NAT10-dependent ac4C modification that stabilizes TNC mRNA (PMID:40158090) and through microRNAs (miR-218, miR-495-3p) that bind the TNC 3'-UTR (PMID:34558654, PMID:36161101); and through RBM10-regulated alternative exon inclusion that generates pro-invasive isoforms. Genetic deletion of TNC in mice establishes essential roles in tendon and bone healing after rotator cuff repair and in early KRAS-driven lung tumor progression. TNC missense mutations co-segregate with DFNA56 nonsyndromic hearing loss, and the protein localizes to the basilar membrane of the cochlea (PMID:23936043).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2011 Medium

    Established that TNC expression is dynamically regulated within the cell cycle rather than constitutive, framing it as an actively controlled gene.

    Evidence TNC promoter–destabilized GFP reporter with single-cell live imaging in NIH 3T3 cells

    PMID:22045641

    Open questions at the time
    • Does not identify the transcription factors driving cell-cycle-dependent activation
    • Single cell type, not validated in disease or primary cells
  2. 2013 Medium

    Linked TNC to a human Mendelian disease, showing that TNC mutations cause inherited hearing loss.

    Evidence Linkage, exome and Sanger sequencing with co-segregation in two Chinese DFNA56 families plus cochlear localization

    PMID:23936043

    Open questions at the time
    • No in vitro functional assay of the missense mutations
    • Mechanism by which TNC supports cochlear function unresolved
  3. 2021 Medium

    Placed TNC upstream of an inflammatory/fibrotic signaling cascade, defining it as a driver rather than a passive ECM marker in diabetic kidney disease.

    Evidence siRNA TNC knockdown in rat mesangial cells with TLR4/NF-κB and CTGF/fibronectin readouts

    PMID:33520106

    Open questions at the time
    • No rescue or receptor-level identification of how TNC engages TLR4
    • Single cellular model without in vivo confirmation
  4. 2021 Medium

    Identified direct microRNA control of TNC and a TNC/AKT/AP-1 feedback loop, connecting post-transcriptional regulation to oncogenic signaling.

    Evidence Dual-luciferase 3'-UTR binding assay for miR-218, AKT/AP-1 readouts, and glioma functional assays

    PMID:34558654

    Open questions at the time
    • Does not define the TNC receptor upstream of AKT
    • Single lab, single tumor type
  5. 2023 Medium

    Defined a super-enhancer mechanism driving TNC, showing transcription factor EN2 binds the TNC SE to activate AKT signaling in lung cancer.

    Evidence H3K27ac ChIP, EN2 gain/loss, AKT phosphorylation, and BET inhibitor JQ1 in NSCLC cells

    PMID:37987507

    Open questions at the time
    • Does not establish how TNC activates AKT mechanistically
    • Single lab
  6. 2024 High

    Resolved an upstream transcriptional cascade (Twist1→Prrx1→TNC) controlling fibroblast activation, with genetic in vivo validation in kidney fibrosis.

    Evidence Promoter-binding assays plus fibroblast-specific Twist1 KO mice in UUO and IRI fibrosis models

    PMID:39181396

    Open questions at the time
    • Does not identify the TNC receptor mediating downstream fibrotic signaling
    • Whether Prrx1 acts solely through TNC is not isolated
  7. 2024 Medium

    Added epigenetic control of TNC, showing TDG-driven DNA demethylation at the TNC locus elevates expression to drive glioma malignancy.

    Evidence ChIP-qPCR, MeDIP-qPCR, and TDG/TNC epistasis rescue in glioma models

    PMID:39090080

    Open questions at the time
    • Does not map the precise demethylated regulatory elements functionally
    • Single lab
  8. 2024 Medium

    Established the integrin/FAK receptor mechanism and an essential in vivo role for TNC in early lung tumorigenesis using genetic deletion.

    Evidence TNC KO in KRAS lung cancer mice with αv integrin blockade and FAK inhibition in vitro (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Relative contribution of αvβ1 versus other integrins not fully dissected
  9. 2024 Medium

    Identified the cellular source (FAPs) and a novel receptor (Annexin A2) for TNC signaling in muscle stem cell self-renewal during repair.

    Evidence Tnc null mice, transcriptomic source mapping, and Annexin A2 receptor identification in muscle regeneration (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Downstream signaling from Annexin A2 not characterized
  10. 2024 Medium

    Demonstrated TNC as a Wnt ligand co-factor, broadening its signaling repertoire beyond integrin and TLR engagement.

    Evidence Wnt reporter assays, ATC xenografts, and spatial in situ hybridization (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular basis of TNC–Wnt ligand binding not structurally defined
  11. 2024 Medium

    Linked alternative splicing of TNC to function, showing RBM10 loss produces a pro-invasive exon-inclusion isoform.

    Evidence RBM10 loss-of-function, isoform-specific knockdown, and in vivo metastasis rescue in thyroid cancer (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanism by which the included exon confers invasiveness unresolved
  12. 2024 Medium

    Established TNC as essential for tendon and bone healing through genetic loss-of-function.

    Evidence Tnc KO rotator cuff repair model with histology, RNA-seq, and biomechanics (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Receptor/pathway mediating the healing role not identified
  13. 2025 Medium

    Defined a post-transcriptional RNA-modification mechanism, showing NAT10-mediated ac4C stabilizes TNC mRNA within an Akt/TGF-β1 feedback loop.

    Evidence acRIP-seq, mRNA stability/translation assays, and rescue experiments in gastric cancer

    PMID:40158090

    Open questions at the time
    • Single lab
    • Does not define the TNC surface receptor activating Akt
  14. 2025 Medium

    Established additional transcriptional and pathogen-driven inputs to TNC, linking ERS/super-enhancer/CREB5 and EBV LMP1 to TNC-dependent EMT and PI3K-Akt signaling.

    Evidence ChIP-seq/CRISPR for CREB5 in HCC and LMP1 expression with PI3K-Akt inhibition in nasopharyngeal carcinoma

    PMID:39915455 PMID:41427845

    Open questions at the time
    • Receptor coupling TNC to PI3K-Akt not defined
    • Single labs per study
  15. 2025 Medium

    Demonstrated therapeutic targeting of TNC, with TNC-CAR-macrophages reducing liver fibrosis by suppressing TLR4/NF-κB and integrin/FAK signaling.

    Evidence TNC-CAR-M phagocytosis assays, CCl4 fibrosis model, CD8 depletion, and Tnc KO comparison

    PMID:41214839

    Open questions at the time
    • Single lab
    • Mechanism of CD8 T cell dependence not fully resolved
  16. 2026 Medium

    Defined a TBX5→TNC→integrin α2/TGF-β axis driving synovial fibroblast fibrosis, extending the integrin-to-TGF-β link to musculoskeletal disease.

    Evidence TBX5 gain/loss, integrin α2 binding assay, Smad2/3 readouts, and in vivo hyperlipidemic rat model

    PMID:41660234

    Open questions at the time
    • Single lab
    • Whether integrin α2 is the sole receptor in this context not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and biochemical basis by which TNC discriminates among its multiple receptors (integrins, TLR4, Annexin A2, Wnt ligands) and how splice/modification isoforms tune receptor selectivity remains unresolved.
  • No structural model of TNC–receptor engagement in the corpus
  • Isoform-specific receptor preferences not mapped
  • Direct biochemical demonstration that TNC binds TLR4 absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0005198 structural molecule activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1266738 Developmental Biology 2
Partners
ANXA2FAKITGA2ITGAVTLR4

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 TNC activates the TLR4/NF-κB p65 signaling pathway in rat mesangial cells under high glucose conditions, leading to upregulation of miR-155-5p, CTGF, and fibronectin; TNC knockdown reduced these downstream effectors, placing TNC upstream of TLR4/NF-κB in a pro-inflammatory and pro-fibrotic loop in diabetic kidney disease. siRNA knockdown of TNC in rat glomerular mesangial cells, Western blot, PCR for TLR4, p-NF-κB p65, miR-155-5p, CTGF, and fibronectin World journal of diabetes Medium 33520106
2024 The transcription factor Twist1 promotes kidney fibroblast activation by directly binding the Prrx1 promoter to drive Prrx1 expression; Prrx1 in turn directly binds the TNC promoter to upregulate TNC. Fibroblast-specific Twist1 deletion in mice reduced Prrx1 and TNC protein levels and attenuated interstitial ECM deposition and kidney inflammation in UUO and ischemia-reperfusion models. Gain- and loss-of-function experiments in rat kidney interstitial fibroblasts; fibroblast-specific Twist1 knockout mice; chromatin-binding/promoter assays; Western blot; mouse kidney fibrosis models (UUO, IRI) Kidney international High 39181396
2025 CREB5 directly binds the TNC promoter and upregulates TNC transcription in hepatocellular carcinoma cells, and this CREB5-driven TNC upregulation promotes epithelial-mesenchymal transition (EMT); endoplasmic reticulum stress activates a super-enhancer that drives CREB5 expression, placing TNC downstream of an ERS/SE/CREB5 axis. ChIP-seq, RNA-seq, CRISPR-Cas9 targeting of CREB5; overexpression and knockdown of CREB5; direct promoter-binding assays; in vitro proliferation, migration, invasion, and EMT assays; in vivo xenograft Cell death & disease Medium 39915455
2008 EMMPRIN overexpression in poorly invasive squamous cell carcinoma (SCC) cells increased TN-C matrix deposition in SCC/peritumor fibroblast co-cultures several-fold; EMMPRIN knockdown by siRNA reduced TN-C deposition to minimal levels. Broad-spectrum MMP inhibitor GM6001 suppressed TN-C deposition in EMMPRIN-overexpressing co-cultures, indicating that EMMPRIN regulates TN-C deposition through MMP activity. Retroviral overexpression of EMMPRIN; siRNA knockdown; SCC/peritumor fibroblast co-culture assays; MMP inhibitor GM6001 treatment; migration assay Anticancer research Medium 18751374
2014 Mechanical stress upregulates TN-C FNIII A1 (an alternatively spliced domain) mRNA and protein in MG-63 osteosarcoma cells via the mTOR pathway; downstream molecules 4E-BP1 and S6K1 were required for normal A1 expression with or without mechanical stress. TN-C FNIII A1 overexpression promoted MG-63 cell migration. Immunohistochemistry of osteosarcoma tissue; mechanical stimulation of MG-63 cells; cell migration assay; mTOR inhibitor treatment; mRNA/protein quantification Molecules and cells Low 24598996
2025 NAT10 promotes N4-acetylcytidine (ac4C) modification of TNC mRNA at specific regions, increasing TNC mRNA stability and translation efficiency, thereby upregulating TNC protein and activating a TNC/Akt/TGF-β1 positive feedback loop that drives gastric cancer cell invasion and proliferation. acRIP-seq; acRIP-qPCR; mRNA stability assays; translation efficiency assays; NAT10 knockdown/overexpression; in vitro and in vivo cancer cell assays; rescue experiments Infectious agents and cancer Medium 40158090
2024 TDG (thymine DNA glycosylase) participates in active DNA demethylation at the TNC locus in glioma cells; TDG binding decreases DNA methylation at the TNC promoter/gene region and elevates TNC expression, which in turn drives glioma malignant phenotype. Simultaneous TNC silencing reduced or reversed glioma promotion caused by TDG overexpression. ChIP-qPCR; MeDIP-qPCR; RNA-seq; TDG and TNC knockdown/overexpression; in vitro and in vivo glioma experiments Cell death discovery Medium 39090080
2023 The m6A demethylase FTO overexpression downregulates both the m6A modification level and mRNA level of TNC in a bleomycin-induced scleroderma mouse model, alleviating skin fibrosis, indicating that FTO negatively regulates TNC expression through m6A demethylation. Adenovirus-mediated FTO overexpression in vivo; m6A quantification; TNC mRNA measurement; histological skin fibrosis scoring; hydroxyproline content Gene Low 37972699
2011 TN-C promoter activity (measured by a destabilized GFP reporter) increases during the last 40% of the cell cycle in individual NIH 3T3 cells, and the magnitude of increase correlates with promoter activity earlier in the cell cycle, demonstrating cell cycle-dependent regulation of TNC expression. Stably transfected TN-C promoter–destabilized GFP reporter cell line; live-cell phase contrast and fluorescence microscopy; automated single-cell tracking over 62 hours Cytometry. Part A Medium 22045641
2025 TNC-targeted CAR-macrophages (TNC-CAR-Ms) specifically phagocytose and kill activated hepatic stellate cells (HSCs) in vitro and reduce liver fibrosis in vivo by decreasing TNC expression and suppressing TLR4/NF-κB and integrin/FAK signaling pathways. The antifibrotic effect required CD8+ T cells, as anti-CD8α antibody depletion significantly impaired TNC-CAR-M efficacy. In vitro phagocytosis/killing assays; CCl4 mouse liver fibrosis model; intravenous TNC-CAR-M administration; Western blot; flow cytometry; RNA-seq; CD8+ T cell depletion experiment; Tnc KO mice comparison Military Medical Research Medium 41214839
2023 MKRN2 protein interacts with STAT1 (demonstrated by Co-IP), and MKRN2 regulates TNC expression via the EBF2 transcription factor in mice; MKRN2 knockout mice show decreased TNC expression in testis, and this is associated with male infertility. MKRN2 knockout mice; Co-IP of MKRN2 and STAT1; Western blot; gene expression analysis in testis and MEF cells Frontiers in endocrinology Low 36967804
2021 miR-218 binds the 3'-UTR of TNC mRNA (validated by dual-luciferase reporter assay) and suppresses TNC expression in glioma cells, reducing AKT phosphorylation and AP-1 transcriptional activity, and downregulating TGFβ1; TGFβ1 can in turn reactivate the TNC/AKT/AP-1 axis, constituting a positive feedback loop that miR-218 disrupts. Dual-luciferase reporter assay for miR-218/TNC 3'-UTR binding; Western blot for AKT, JNK phosphorylation; TGFβ1 expression analysis; in vitro and in vivo glioma cell functional assays International journal of molecular medicine Medium 34558654
2023 EN2 (Engrailed 2) directly binds the super-enhancer (SE) region in the TNC gene locus (enriched with H3K27ac) and drives TNC expression, which in turn activates AKT signaling (AKT-Ser473 phosphorylation) in non-small cell lung cancer cells; JQ1 (BET SE inhibitor) abolished EN2-driven TNC expression and AKT phosphorylation. ChIP for H3K27ac at TNC SE; EN2 overexpression/knockdown; TNC expression measurement; AKT phosphorylation Western blot; JQ1 pharmacological inhibition Environmental toxicology Medium 37987507
2022 miR-495-3p directly targets TNC (validated by luciferase reporter assay); TNC silencing in H9C2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) reduced Ca2+ overload, restored mitochondrial membrane potential, and decreased apoptosis and inflammatory cytokines. miR-495-3p depletion worsened H/R injury, and TNC silencing reversed this effect. Luciferase reporter assay; siRNA TNC silencing; miR-495-3p inhibitor transfection; CCK-8; flow cytometry; Ca2+ and MMP measurements; ELISA; qRT-PCR; Western blot Regenerative therapy Medium 36161101
2025 EBV-encoded LMP1 upregulates TNC expression in nasopharyngeal carcinoma cells; TNC activates PI3K-Akt signaling to promote tumor cell proliferation, survival, migration, and in vivo growth. TNC knockdown or PI3K-Akt inhibition significantly reversed LMP1-driven malignant progression in vitro and in vivo. Lentiviral LMP1 stable expression; TNC knockdown; PI3K-Akt inhibitor; in vitro proliferation/migration assays; in vivo xenograft FASEB journal Medium 41427845
2026 TBX5 transcriptionally promotes TNC expression; TNC then binds integrin α2 (Itgα2) on fibroblasts and activates the TGF-β/Smad2/3 signaling pathway, driving synovial fibroblast fibrosis in frozen shoulder. In vivo TBX5 targeting mitigated mobility loss and joint capsule fibrosis in hyperlipidemic rats. Transcriptomics; TBX5 overexpression/knockdown; TNC expression measurement; integrin α2 binding assay; TGF-β/Smad2/3 pathway Western blot; in vivo hyperlipidemic rat model with TBX5 targeting iScience Medium 41660234
2024 Genetic deletion of TNC (Tnc null mice) impairs tendon and bone healing after rotator cuff repair, reduces post-repair activity levels, and alters gene expression in the shoulder including upregulation of sex hormone and WNT pathways and downregulation of inflammation and cell cycle pathways, indicating TNC is required for normal tendon healing responses. Tnc knockout and heterozygous knock-in mouse rotator cuff repair model; histology; RNA-seq; biomechanical testing; activity wheel monitoring bioRxivpreprint Medium
2024 TNC stimulates lung adenocarcinoma (LUAD) tumor cell proliferation and migration through engagement of αv-containing integrins (specifically integrin αvβ1) and subsequent focal adhesion kinase (FAK) activation; genetic deletion of TNC in KRAS-driven mouse lung cancer models reduced early tumor burden, high-grade pathology, tumor cell proliferation, invasion, and FAK activity. TNC genetic deletion in oncogenic KRAS lung cancer mouse models; in vitro cell proliferation/migration assays with αv integrin blockade and FAK inhibition; FAK phosphorylation measurements; histopathology bioRxivpreprint Medium
2024 Fibro-adipogenic progenitors (FAPs) are the primary cellular source of TNC during muscle repair; muscle stem cells (MuSC) sense TNC signaling through the cell surface receptor Annexin A2. Mice lacking TNC exhibit a premature aging regeneration phenotype, and TNC is proposed to decline in physiological aging contributing to inefficient muscle regeneration. In vivo mouse muscle repair models with Tnc null mice; single-cell/bulk transcriptomics identifying FAPs as TNC source; Annexin A2 receptor identification; regeneration phenotype characterization bioRxivpreprint Medium
2024 TNC binds Wnt ligands and potentiates ligand-dependent Wnt signaling in thyroid cancer; in anaplastic thyroid cancer (ATC) mouse xenograft models, TNC increased Wnt signaling, tumor burden, invasion, and metastasis. Spatially, TNC was enriched at the invasive edge adjacent to Wnt ligand-producing fibroblasts. In vitro Wnt reporter assays with TNC; ATC NOD-SCID mouse xenograft model; RNA in situ hybridization for spatial localization; bulk RNA-sequencing from patient cohorts bioRxivpreprint Medium
2024 RBM10 loss leads to exon inclusion events in TNC mRNA (along with VCL and CD44); the TNC exon-inclusion isoform specifically promotes invasiveness of thyroid cancer cells. Combined knockdown of VCL, CD44, and TNC inclusion isoforms reversed metastases in Hras G12V/Rbm10 KO thyrocyte mouse models. RBM10 loss-of-function in thyroid cancer cells and mouse models; transcriptome analysis of exon-inclusion events; siRNA knockdown of TNC exon-inclusion isoform; in vitro invasion assays; in vivo mouse metastasis model bioRxivpreprint Medium
2013 TNC gene mutations co-segregating with hearing loss were identified in two Chinese families: missense mutation c.5317G>A (p.V1773M) and c.5368A>T (p.T1796S), both located in a conserved region and predicted deleterious. TNC protein is present in the basilar membrane and osseous spiral lamina of the cochlea, establishing TNC as the causative gene for DFNA56 nonsyndromic hearing loss. Linkage analysis; whole exome sequencing; Sanger sequencing; co-segregation analysis in 53 family members; mass spectrum genotyping; SIFT functional prediction PloS one Medium 23936043
2024 ACE2 negatively regulates TNC expression in keratinocytes (HaCaT cells); ACE2 knockdown or pharmacological inhibition upregulated TNC and activated PI3K/AKT/mTOR signaling, enhancing cell proliferation and migration. In vivo, topical ACE2 inhibition in a rat tissue expansion model increased epidermal thickness, keratinocyte proliferation, TNC expression, and PI3K/AKT/mTOR activity. ACE2 siRNA knockdown; ACE2 inhibitor MLN-4760; ACE2 overexpression plasmid; transcriptomic sequencing identifying TNC as key DEG; EdU proliferation assay; wound healing assay; Western blot for TNC/PI3K/AKT/mTOR; in vivo rat skin expansion model with histology and PCNA immunofluorescence Pathology, research and practice Medium 41980472

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 The effects of partial extraction of TnC upon the tension-pCa relationship in rabbit skinned skeletal muscle fibers. The Journal of general physiology 120 4056736
1997 Resistance to salmonellosis in the chicken is linked to NRAMP1 and TNC. Genome research 101 9253598
1997 A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV-1(89.6) but not the T-tropic isolate HIV-1(HxB). Journal of virology 62 9188648
2015 Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer. Nucleic acids research 56 25609695
2003 Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics. Journal of applied physiology (Bethesda, Md. : 1985) 53 12736193
2021 Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-κB/miR-155-5p inflammatory loop. World journal of diabetes 52 33520106
2013 Exome sequencing and linkage analysis identified tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss. PloS one 46 23936043
2000 Comparison of the sequences of the Aspergillus nidulans hxB and Drosophila melanogaster ma-l genes with nifS from Azotobacter vinelandii suggests a mechanism for the insertion of the terminal sulphur atom in the molybdopterin cofactor. Molecular microbiology 45 11029694
2012 Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 43 23192621
1983 Demonstration of keratin filaments in thymic nurse cells (TNC) and alloreactivity of TNC-T cell population. Thymus 42 6189269
2016 Candidate gene approach identifies six SNPs in tenascin-C (TNC) associated with degenerative rotator cuff tears. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 38 27248364
2008 CPA6, FMO2, LGI1, SIAT1 and TNC are differentially expressed in early- and late-stage oral squamous cell carcinoma--a pilot study. Oral oncology 36 18234543
2020 Novel ASAP1-USP6, FAT1-USP6, SAR1A-USP6, and TNC-USP6 fusions in primary aneurysmal bone cyst. Genes, chromosomes & cancer 34 32011035
2018 Kynurenic Acid Inhibits the Electrical Stimulation Induced Elevated Pituitary Adenylate Cyclase-Activating Polypeptide Expression in the TNC. Frontiers in neurology 30 29387039
2001 Mapping the interacting regions between troponins T and C. Binding of TnT and TnI peptides to TnC and NMR mapping of the TnT-binding site on TnC. The Journal of biological chemistry 27 11473120
1975 Molecular and biological studies on cardiac muscle calcium-binding protein (TN-C). Canadian journal of biochemistry 27 123476
2012 Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel. Genome biology 25 22541052
2011 Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease. Human genetics 25 21298289
2022 Temporal characteristics of astrocytic activation in the TNC in a mice model of pain induced by recurrent dural infusion of inflammatory soup. The journal of headache and pain 24 35033010
2019 Upregulation of microRNA-9-5p inhibits apoptosis of chondrocytes through downregulating Tnc in mice with osteoarthritis following tibial plateau fracture. Journal of cellular physiology 23 31169312
2001 Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC). Cephalalgia : an international journal of headache 22 11298663
1995 Assignment of the tenascin gene (HXB) to swine chromosome 1q21.1-->q21.3 by fluorescence in situ hybridization. Cytogenetics and cell genetics 22 7530615
2013 Adult teleost heart expresses two distinct troponin C paralogs: cardiac TnC and a novel and teleost-specific ssTnC in a chamber- and temperature-dependent manner. Physiological genomics 21 23881286
1999 The hxB gene, necessary for the post-translational activation of purine hydroxylases in Aspergillus nidulans, is independently controlled by the purine utilization and the nicotinate utilization transcriptional activating systems. Molecular microbiology 21 10096075
2013 mRNA distribution of CGRP and its receptor components in the trigeminovascular system and other pain related structures in rat brain, and effect of intracerebroventricular administration of CGRP on Fos expression in the TNC. Neuroscience letters 20 24321404
2008 EMMPRIN modulates migration and deposition of TN-C in oral squamous carcinoma. Anticancer research 20 18751374
1984 Helper T cell activity demonstrated by thymic nurse T cells (TNC-T). Immunology 20 6229473
2021 Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report. Diagnostic pathology 18 34256767
2025 Endoplasmic reticulum stress-related super enhancer promotes epithelial-mesenchymal transformation in hepatocellular carcinoma through CREB5 mediated activation of TNC. Cell death & disease 17 39915455
2024 Transcription factor Twist1 drives fibroblast activation to promote kidney fibrosis via signaling proteins Prrx1/TNC. Kidney international 17 39181396
2002 Genome scanning of the HXB/BXH sets of recombinant inbred strains of the rat for quantitative trait loci associated with conditioned taste aversion. Behavior genetics 17 11958542
2011 Cell cycle dependent TN-C promoter activity determined by live cell imaging. Cytometry. Part A : the journal of the International Society for Analytical Cytology 16 22045641
1991 Thymic nurse cells (TNC) in spontaneous thymoma BUF/Mna rats as a model to study their roles in T-cell development. Immunology 16 2071160
2021 MicroRNA‑218 inhibits the malignant phenotypes of glioma by modulating the TNC/AKT/AP‑1/TGFβ1 feedback signaling loop. International journal of molecular medicine 14 34558654
2013 Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses. Equine veterinary journal 14 23906005
2017 Myosin Rod Hypophosphorylation and CB Kinetics in Papillary Muscles from a TnC-A8V KI Mouse Model. Biophysical journal 13 28445763
2014 mTOR signal transduction pathways contribute to TN-C FNIII A1 overexpression by mechanical stress in osteosarcoma cells. Molecules and cells 13 24598996
1992 Comparative mapping of mouse chromosome 4 and human chromosome 9: Lv, Orm, and Hxb are closely linked on mouse chromosome 4. Mammalian genome : official journal of the International Mammalian Genome Society 12 1379092
2025 Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma. Journal of translational medicine 9 40598496
2025 TNC-targeted CAR-macrophage therapy alleviates liver fibrosis in mice. Military Medical Research 9 41214839
2024 RNA-seq analysis and in vivo experiments identified the protective effect of kaempferol on idiopathic pulmonary fibrosis by regulating the PPARG/TNC signaling pathway to reduce ECM deposition. Food & function 9 39587935
2022 MiR-495-3p depletion contributes to myocardial ischemia/reperfusion injury in cardiomyocytes by targeting TNC. Regenerative therapy 9 36161101
2018 Are TNC gene variants associated with anterior cruciate ligament rupture susceptibility? Journal of science and medicine in sport 9 30528246
1998 Tenascin-cytotactin (TN-C) variants in pseudophakic/aphakic bullous keratopathy corneas. Eye (London, England) 9 9850274
1994 The cardiac Ca(2+)-deficient EF-hand governs the phenotype of the cardiac-skeletal TnC-chimera in solution by Sr(2+)-induced tryptophan fluorescence emission. Biochemistry 9 8049206
2023 Characteristics of n6-methyladenosine (m6A) regulators and role of FTO/TNC in scleroderma. Gene 8 37972699
2016 Functional Divergence in Teleost Cardiac Troponin Paralogs Guides Variation in the Interaction of TnI Switch Region with TnC. Genome biology and evolution 8 26979795
2024 The role of TNC in atherosclerosis and drug development opportunities. International journal of biological sciences 7 38164188
2018 TnI Structural Interface with the N-Terminal Lobe of TnC as a Determinant of Cardiac Contractility. Biophysical journal 7 29642034
2024 TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation. Cell death discovery 6 39090080
2021 Cellular Fibroma of Tendon Sheath With Novel TNC-USP6 Gene Fusion Clinically Mimicking Arthritis in a 7-Year-Old Boy. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 6 34520696
2022 Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose. PLoS genetics 5 35377872
2011 Expression and functional characterisation of TNC, a high-affinity nickel transporter from Neurospora crassa. Fungal genetics and biology : FG & B 5 21840412
2025 NAT10 promotes gastric cancer progression by enhancing the N4-acetylcytidine modification of TNC mRNA. Infectious agents and cancer 4 40158090
2022 Beyond Genes: Inclusion of Alternative Splicing and Alternative Polyadenylation to Assess the Genetic Architecture of Predisposition to Voluntary Alcohol Consumption in Brain of the HXB/BXH Recombinant Inbred Rat Panel. Frontiers in genetics 4 35368676
2020 High Frequencies of TNC and COL5A1 Genotypes Associated With Low Risk for Superficial Digital Flexor Tendinopathy in Greek Indigenous Horse Breeds Compared With Warmblood Horses. Journal of equine veterinary science 4 32797795
2024 A novel splice-altering TNC variant (c.5247A > T, p.Gly1749Gly) in an Chinese family with autosomal dominant non-syndromic hearing loss. BMC medical genomics 3 39020321
2023 MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression. Frontiers in endocrinology 3 36967804
2022 LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients. Biomarkers in medicine 3 35786977
2020 Molecular characterization of troponin C (TnC) in Scylla paramamosain and its role in white spot syndrome virus and Vibrio alginolyticus infection. Fish & shellfish immunology 3 31911290
2008 Effect of maternal age, birth weight and infant sex on total nucleated cell (TNC) count and volume of umbilical cord blood (UCB) collected. The Medical journal of Malaysia 3 19024981
2025 Trained mesenchymal stromal cell-based therapy HXB-319 for treating diffuse alveolar hemorrhage in a pristane-induced murine model. Stem cells (Dayton, Ohio) 2 39560076
2023 Engrailed 2 serves as a master regulator of the super-enhancer in the TNC gene locus in non-small cell lung cancer. Environmental toxicology 2 37987507
1991 [Phenotypic and functional analysis of thymic nurse cell (TNC)-lymphocytes]. Wiener klinische Wochenschrift 2 2024527
2025 A novel trained mesenchymal stromal cell-based therapy, HXB-319, effectively controls progressive glomerulonephritis in a murine lupus model. Stem cells (Dayton, Ohio) 1 40588433
2025 Synergistic Efficacy of Chidamide and LB100 in Sézary Syndrome via TNC Downregulation and PI3K/AKT/mTOR Dephosphorylation. Cancer science 1 40903394
2025 EBV-LMP1 Promotes the Progression of Nasopharyngeal Carcinoma via TNC-Mediated Activation of PI3K/Akt Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41427845
2024 PMMA-induced biofilm promotes Schwann cells migration and proliferation mediated by EGF/Tnc/FN1 to improve sciatic nerve defect. Heliyon 1 39296039
2023 Associations between prefrontal PI (16:0/20:4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain. Frontiers in psychiatry 1 37143779
2012 Postmortem serum tenascin-C (TN-C) concentrations in forensic autopsy cases: A pilot study. Legal medicine (Tokyo, Japan) 1 23043956
2026 hsa_circ_0006168 drives microglial activation in TNC via miR-99b-5p/KDM6B axis to promote central sensitization in migraine. The journal of headache and pain 0 41654728
2026 Hyperlipidemia exacerbates frozen shoulder fibrosis by activating the TGF-β/Smad2/3 signaling pathway via the TBX5-TNC-Itgα2 axis. iScience 0 41660234
2026 ACE2 impairs epidermal regeneration by inhibiting TNC expression and PI3K/AKT/mTOR signaling. Pathology, research and practice 0 41980472
2025 TNC and GJA1 Are Putative Progenitor Markers That Are Localized in the Perivascular Adventitia of the Adult Monkey Brain Subventricular Niche. International journal of molecular sciences 0 40003865
2025 GJB2 promotes ovarian cancer progression and cisplatin resistance by upregulating TNC expression. Biochimica et biophysica acta. Molecular cell research 0 40915501
2025 Single-cell and spatial transcriptomics reveal TNC-positive cancer-associated fibroblasts that mediate immunosuppression and promote tumor progression in basal cell carcinoma. Journal of translational medicine 0 41310748
2025 MicroRNA-9-5p regulates apoptosis of human osteoarthritis chondrocytes through suppressing TnC. African health sciences 0 41640526
2024 Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss. Medicine 0 38640279
2024 Quantitative proteomic landscape of the pathophysiology of adhesive arachnoiditis and its clinical significance: Structure and mechanism of TNC and RANBP1 proteins. International journal of biological macromolecules 0 39662555

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