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Fibroblast growth factor\u20101 (\n FGF<\/jats:styled-content>\n \u20101) belongs to the\n FGF<\/jats:styled-content>\n family and has been shown to inhibit fibroblast collagen production and differentiation into myofibroblasts, and revert epithelial\u2013mesenchymal transition by inhibiting\n TGF<\/jats:styled-content>\n \u2010\u03b21 signalling pathways. However, the precise role of\n FGF<\/jats:styled-content>\n \u20101 in pulmonary fibrosis has not yet been elucidated. In this study, we explore the mechanisms underlying the anti\u2010fibrogenic effect of\n FGF<\/jats:styled-content>\n \u20101 in pulmonary fibrosis\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n by prolonged transient overexpression of\n FGF<\/jats:styled-content>\n \u20101 (\n AdFGF<\/jats:styled-content>\n \u20101) and\n TGF<\/jats:styled-content>\n \u2010\u03b21 (\n AdTGF<\/jats:styled-content>\n \u2010\u03b21) using adenoviral vectors.\n In vivo<\/jats:italic>\n ,\n FGF<\/jats:styled-content>\n \u20101 overexpression markedly attenuated\n TGF<\/jats:styled-content>\n \u2010\u03b21\u2010induced pulmonary fibrosis in rat lungs when given both concomitantly, or delayed, by enhancing proliferation and hyperplasia of alveolar epithelial cells (\n AECs<\/jats:styled-content>\n ).\n AdFGF<\/jats:styled-content>\n \u20101 also attenuated the\n TGF<\/jats:styled-content>\n \u2010\u03b21 signalling pathway and induced\n FGFR1<\/jats:styled-content>\n expression in\n AECs<\/jats:styled-content>\n .\n In vitro<\/jats:italic>\n ,\n AdFGF<\/jats:styled-content>\n \u20101 prevented the increase in \u03b1\u2010\n SMA<\/jats:styled-content>\n and the decrease in E\u2010cadherin induced by\n AdTGF<\/jats:styled-content>\n \u2010\u03b21 in normal human lung fibroblasts, primary human pulmonary\n AECs<\/jats:styled-content>\n , and\n A549<\/jats:styled-content>\n cells. Concomitantly,\n AdTGF<\/jats:styled-content>\n \u2010\u03b21\u2010induced Smad2 phosphorylation was significantly reduced by\n AdFGF<\/jats:styled-content>\n \u20101 in both cell types.\n AdFGF<\/jats:styled-content>\n \u20101 also attenuated the increase in\n TGF\u03b2R1<\/jats:styled-content>\n protein and\n mRNA<\/jats:styled-content>\n levels in fibroblasts. In\n AECs<\/jats:styled-content>\n ,\n AdFGF<\/jats:styled-content>\n \u20101 decreased\n TGF\u03b2R1<\/jats:styled-content>\n protein by favouring\n TGF\u03b2R1<\/jats:styled-content>\n degradation through the caveolin\u20101\/proteasome pathway. Furthermore,\n FGFR1<\/jats:styled-content>\n expression was increased in\n AECs<\/jats:styled-content>\n , whereas it was decreased in fibroblasts. In serum of\n IPF<\/jats:styled-content>\n patients,\n FGF<\/jats:styled-content>\n \u20101 levels were increased compared to controls. Interestingly,\n FGF<\/jats:styled-content>\n \u20101 expression was restricted to areas of\n AEC<\/jats:styled-content>\n hyperplasia, but not \u03b1\u2010\n SMA<\/jats:styled-content>\n \u2010positive areas in\n IPF<\/jats:styled-content>\n lung tissue. Our results demonstrate that\n FGF<\/jats:styled-content>\n \u20101 may have preventative and therapeutic effects on\n TGF<\/jats:styled-content>\n \u2010\u03b21\u2010driven pulmonary fibrosis via inhibiting myofibroblast differentiation, inducing\n AEC<\/jats:styled-content>\n proliferation, regulating\n TGF<\/jats:styled-content>\n \u2010\u03b21 signalling by controlling\n TGF\u03b2R1<\/jats:styled-content>\n expression and degradation, and regulating\n FGFR1<\/jats:styled-content>\n expression. Thus, modulating\n FGF<\/jats:styled-content>\n \u20101 signalling represents a potential therapy for the treatment of pulmonary fibrosis. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4768","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T06:42:14Z","timestamp":1468824134000},"page":"197-210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Fibroblast growth factor\u20101 attenuates\n TGF<\/scp>\n \u2010\u03b21\u2010induced lung fibrosis"],"prefix":"10.1002","volume":"240","author":[{"given":"Chiko","family":"Shimbori","sequence":"first","affiliation":[{"name":"Firestone Institute for Respiratory Health, Departments of Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Simon","family":"Bellaye","sequence":"additional","affiliation":[{"name":"Firestone Institute for Respiratory Health, Departments of Medicine McMaster University Hamilton Ontario 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