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http://purl.uniprot.org/citations/18096707http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18096707http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen.

Objectives

To investigate the role of EDA-containing fibronectin in lung fibrogenesis.

Methods

Primary lung fibroblasts from patients with idiopathic pulmonary fibrosis or from patients undergoing resection for lung cancer were assessed for EDA-containing fibronectin and alpha-smooth muscle actin (alpha-SMA) expression. Mice lacking the EDA domain of fibronectin and their wild-type littermates were challenged with the bleomycin model of lung fibrosis. Primary lung fibroblasts from these mice were assayed in vitro to determine the contribution of EDA-containing fibronectin to fibroblast phenotypes.

Measurements and main results

Idiopathic pulmonary fibrosis lung fibroblasts produced markedly more EDA-containing fibronectin and alpha-SMA than control fibroblasts. EDA-null mice failed to develop significant fibrosis 21 days after bleomycin challenge, whereas wild-type controls developed the expected increase in total lung collagen. Histologic analysis of EDA-null lungs after bleomycin showed less collagen and fewer alpha-SMA-expressing myofibroblasts compared with that observed in wild-type mice. Failure to develop lung fibrosis in EDA-null mice correlated with diminished activation of latent transforming growth factor (TGF)-beta and decreased lung fibroblast responsiveness to active TGF-beta in vitro.

Conclusions

The data show that EDA-containing fibronectin is essential for the fibrotic resolution of lung injury through TGF-beta activation and responsiveness, and suggest that EDA-containing fibronectin plays a critical role in tissue fibrogenesis."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.org/dc/terms/identifier"doi:10.1164/rccm.200708-1291oc"xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Yan M."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Baralle F.E."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Sheppard D."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Muro A.F."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"White E.S."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Moretti F.A."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Toews G.B."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Martinez F.J."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Wilke C.A."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Moore B.B."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Flaherty K.R."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Atrasz R.G."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/author"Tsui J.L."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/name"Am J Respir Crit Care Med"xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/pages"638-645"xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/title"An essential role for fibronectin extra type III domain A in pulmonary fibrosis."xsd:string
http://purl.uniprot.org/citations/18096707http://purl.uniprot.org/core/volume"177"xsd:string
http://purl.uniprot.org/citations/18096707http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18096707
http://purl.uniprot.org/citations/18096707http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18096707
http://purl.uniprot.org/uniprot/#_A0A087WQE0-mappedCitation-18096707http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18096707
http://purl.uniprot.org/uniprot/#_A0A087WS56-mappedCitation-18096707http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18096707
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