ArticleJournal of cell science2018
The fibronectin ED-A domain enhances recruitment of latent TGF-β-binding protein-1 to the fibroblast matrix.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 165 citations in OpenAlex.
- Multimodal profiling establishes ovarian fibrosis as a measurable and targetable hallmark of human reproductive aging.Research square · 2026Article
- Multi-omics Analysis Reveals the Prognostic and Therapeutic Value of TGF-β Signaling-related Genes in Idiopathic Pulmonary Fibrosis.Biochemical genetics · 2026Article
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- Certain role of extra-domain A containing fibronectin in the development of pulmonary hypertension in the sugen/hypoxia mouse model.Cardiovascular diagnosis and therapy · 2026Article
- The ADAMTS family: from extracellular matrix proteases to orchestrators of fibrosis.Cell communication and signaling : CCS · 2026Review
- Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity.NPJ Regenerative medicine · 2026Article
- Baicalein attenuates extracellular matrix remodeling via FN1 in diabetic kidney disease: a multi-omics, machine-learning and mesangial-cell rescue study.Frontiers in pharmacology · 2026Article
- BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Circular RNAs in Diabetic Foot Ulcers: A Scoping Review of Clinical, Preclinical, and In Silico Evidence on Diagnostic and Therapeutic Potentials.Endocrinology, diabetes & metabolism · 2026Article
- Integrin α4 and α9 in trabecular meshwork and Schlemm's canal function: emerging regulators of intraocular pressure homeostasis.Frontiers in cell and developmental biology · 2026Review
- Biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluid and saliva. Study methods and pathophysiological significance.Frontiers in medicine · 2026Review
- Multi-omics factor analysis identifies the Tensin 1-Fermitin family homologue 2-Fibronectin 1-Integrin signaling axis as a prognostic determinant in colorectal cancer.Molecular biomedicine · 2025Article
- Persistent tissue regeneration and transforming growth factor-β induced fibrosis in the masseter muscle of mdxScientific reports · 2025Article
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts.Scientific reports · 2025Article
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.Respiratory research · 2025Article
- Lactic acid metabolism: gynecological cancer's Achilles' heel.Discover oncology · 2025Review
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Dysregulated secretion and extracellular activation of TGF-β1 stimulates myofibroblasts to accumulate disordered and stiff extracellular matrix (ECM) leading to fibrosis. Fibronectin immobilizes latent TGF-β-binding protein-1 (LTBP-1) and thus stores TGF-β1 in the ECM. Because the ED-A fibronectin splice variant is prominently expressed during fibrosis and supports myofibroblast activation, we investigated whether ED-A promotes LTBP-1-fibronectin interactions. Using stiffness-tuneable substrates for human dermal fibroblast cultures, we showed that high ECM stiffness promotes expression and colocalization of LTBP-1 and ED-A-containing fibronectin. When rescuing fibronectin-depleted fibroblasts with specific fibronectin splice variants, LTBP-1 bound more efficiently to ED-A-containing fibronectin than to ED-B-containing fibronectin and fibronectin lacking splice domains. Function blocking of the ED-A domain using antibodies and competitive peptides resulted in reduced LTBP-1 binding to ED-A-containing fibronectin, reduced LTBP-1 incorporation into the fibroblast ECM and reduced TGF-β1 activation. Similar results were obtained by blocking the heparin-binding stretch FNIII12-13-14 (HepII), adjacent to the ED-A domain in fibronectin. Collectively, our results suggest that the ED-A domain enhances association of the latent TGF-β1 by promoting weak direct binding to LTBP-1 and by enhancing heparin-mediated protein interactions through HepII in fibronectin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.