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http://purl.uniprot.org/citations/29361522http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29361522http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.org/dc/terms/identifier"doi:10.1242/jcs.201293"xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Lodyga M."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Koehler A."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"White E.S."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Wells R.G."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Hinz B."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Im M."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Olsen A.L."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Boo S."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Chow M.L."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Klingberg F."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Chau G."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/author"Walraven M."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/name"J Cell Sci"xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/pages"jcs201293"xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/title"The fibronectin ED-A domain enhances recruitment of latent TGF-beta-binding protein-1 to the fibroblast matrix."xsd:string
http://purl.uniprot.org/citations/29361522http://purl.uniprot.org/core/volume"131"xsd:string
http://purl.uniprot.org/citations/29361522http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29361522
http://purl.uniprot.org/citations/29361522http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29361522
http://purl.uniprot.org/uniprot/#_A0A078BBI5-mappedCitation-29361522http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29361522
http://purl.uniprot.org/uniprot/#_A0A078BC11-mappedCitation-29361522http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29361522
http://purl.uniprot.org/uniprot/#_A0A078BCJ0-mappedCitation-29361522http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29361522