title: Basic fibroblast growth factor activates β-catenin/RhoA signaling in pulmonary fibroblasts with chronic obstructive pulmonary disease in rats.
abstract: Chronic obstructive pulmonary disease (COPD) is featured by aberrant extracellular matrix (ECM) deposition. Trigger of the β-catenin/RhoA pathway has been involved in aberrant ECM deposition in several diseases. We investigated WNT signaling activation in primary pulmonary fibroblasts of rats with and without COPD and the function of WNT signaling in pulmonary fibroblast. We evaluated the expression of WNT signaling and the role of β-catenin, using MRC-5 fibroblasts and primary lung fibroblasts of rats with and without COPD. Lung fibroblasts highly expressed mRNA of genes associated with WNT signaling. Treatment of MRC-5 fibroblasts using basic fibroblast growth factor (bFGF), a composition of the mucus in COPD patients, enhanced β-catenin, Wnt5a and RhoA expression. The expression in β-catenin, Wnt5a and RhoA induced by bFGF was higher in fibroblasts of rats with COPD than without COPD, whereas the basal expression was similar. bFGF also activated transcriptionally active and increased total β-catenin protein expression. Moreover, bFGF enhanced the expression of α-sm-actin and fibronectin, which was abrogated by β-catenin, Wnt5a and RhoA-specific adenovirus siRNA. The induction of active β-catenin and then fibronectin turnover in response to bFGF were markedly increased in pulmonary fibroblasts from rat with COPD. β-Catenin/RhoA pathway results in ECM deposition in lung fibroblasts and myofibroblasts differentiation. β-catenin/RhoA signaling induced by bFGF is promoted in lung fibroblasts from rats with COPD. The study indicated a crucial role of the WNT signaling in mediating fibroblast morphology and function in COPD.
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Nanming, Guiyang, 550001, Guizhou, China. u.wlake@gmail.com.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Nanming, Guiyang, 550001, Guizhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Nanming, Guiyang, 550001, Guizhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Nanming, Guiyang, 550001, Guizhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Guiyang College of Traditional Chinese Medicine, 50 Shidong Road, Nanming, Guiyang, 550001, Guizhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; D020742:rhoA GTP-Binding Protein
keywords: Basic fibroblast growth factor; Chronic obstructive pulmonary disease; MRC-5 fibroblasts; β-Catenin