title: Inhibition of α-SMA by the ectodomain of FGFR2c attenuates lung fibrosis.
abstract: The soluble ectodomain of fibroblast growth factor receptor-IIIc (sFGFR2c) is able to bind to fibroblast growth factor (FGF) ligands and block the activation of the FGF-signaling pathway. In this study, sFGFR2c inhibited lung fibrosis dramatically in vitro and in vivo. The upregulation of α-smooth muscle actin (α-SMA) in fibroblasts by transforming growth factor-β1 (TGF-β1) is an important step in the process of lung fibrosis, in which FGF-2, released by TGF-β1, is involved. sFGFR2c inhibited α-SMA induction by TGF-β1 via both the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad3 pathways in primary mouse lung fibroblasts and the proliferation of mouse lung fibroblasts. In a mouse model of bleomycin (BLM)-induced lung fibrosis, mice were treated with sFGFR2c from d 3 or d 10 to 31 after BLM administration. Then we used hematoxylin and eosin staining, Masson staining and immunohistochemical staining to evaluate the inhibitory effects of sFGFR2c on lung fibrosis. The treatment with sFGFR2c resulted in significant attenuation of the lung fibrosis score and collagen deposition. The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.
authors.affiliation: Guangdong Provincial Key Laboratory of Bioengineering Medicine (National Engineering Research Centre of Genetic Medicine), Guangzhou, Guangdong China. wang_ju1688@yahoo.cn
authors.forename: Wang
authors.initials: W
authors.lastname: Ju
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhihong
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhiyou
authors.forename: Huang
authors.initials: H
authors.lastname: Qin
authors.forename: Wang
authors.initials: W
authors.lastname: Dingding
authors.forename: Sun
authors.initials: S
authors.lastname: Li
authors.forename: Zhu
authors.initials: Z
authors.lastname: Baowei
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: He
authors.initials: H
authors.lastname: Ying
authors.forename: Hong
authors.initials: H
authors.lastname: An
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001761:Bleomycin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000150:complications / Q000235:genetics / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000737:chemistry* / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000199:Actins; D020033:Protein Isoforms; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D016222:Fibroblast Growth Factor 2; D001761:Bleomycin; D051497:Receptor, Fibroblast Growth Factor, Type 2