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首页> 外文期刊>Molecular and Cellular Biochemistry: An International Journal for Chemical Biology >Basic fibroblast growth factor activates beta-catenin/RhoA signaling in pulmonary fibroblasts with chronic obstructive pulmonary disease in rats
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Basic fibroblast growth factor activates beta-catenin/RhoA signaling in pulmonary fibroblasts with chronic obstructive pulmonary disease in rats

机译:碱性成纤维细胞生长因子激活大鼠慢性阻塞性肺疾病的肺成纤维细胞中的β-catenin/ RhoA信号

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Chronic obstructive pulmonary disease (COPD) is featured by aberrant extracellular matrix (ECM) deposition. Trigger of the beta-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 beta-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 beta-catenin, Wnt5a and RhoA expression. The expression in beta-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 beta-catenin protein expression. Moreover, bFGF enhanced the expression of alpha-sm-actin and fibronectin, which was abrogated by beta-catenin, Wnt5a and RhoA-specific adenovirus siRNA. The induction of active beta-catenin and then fibronectin turnover in response to bFGF were markedly increased in pulmonary fibroblasts from rat with COPD. beta-Catenin/RhoA pathway results in ECM deposition in lung fibroblasts and myofibroblasts differentiation. beta-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.
机译:慢性阻塞性肺疾病(COPD)的特征是细胞外基质(ECM)异常沉积。 β-catenin/ RhoA途径的触发已参与多种疾病的异常ECM沉积。我们调查了有和没有COPD的大鼠原代肺成纤维细胞中WNT信号的激活以及肺成纤维细胞中WNT信号的功能。我们使用和不使用COPD的大鼠使用MRC-5成纤维细胞和原代肺成纤维细胞评估了WNT信号的表达和β-连环蛋白的作用。肺成纤维细胞高表达与WNT信号相关的基因的mRNA。使用碱性成纤维细胞生长因子(bFGF)来治疗MRC-5成纤维细胞,这是COPD患者的黏液成分,增强了β-catenin,Wnt5a和RhoA的表达。 bFGF诱导的COPD大鼠成纤维细胞中β-catenin,Wnt5a和RhoA的表达高于无COPD的大鼠,而基础表达相似。 bFGF还激活了转录活性并增加了总β-catenin蛋白的表达。此外,bFGF增强了α-sm-actin和纤连蛋白的表达,β-catenin,Wnt5a和RhoA特异性腺病毒siRNA消除了它们。在患有COPD的大鼠的肺成纤维细胞中,响应于bFGF的活性β-catenin诱导,然后纤连蛋白更新明显增加。 β-Catenin/ RhoA途径导致ECM在肺成纤维细胞中沉积并分化为成肌纤维细胞。 bFGF诱导的β-catenin/ RhoA信号在患有COPD的大鼠的肺成纤维细胞中得到促进。该研究表明WNT信号传导在COPD中介导成纤维细胞形态和功能中起着至关重要的作用。

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