法尼甾体X受体
鹅去氧胆酸
脱氧胆酸
胆汁酸
成纤维细胞
癌症研究
上皮-间质转换
A549电池
肺纤维化
肺
医学
下调和上调
细胞生物学
内科学
内分泌学
化学
生物
生物化学
核受体
体外
转录因子
基因
作者
Chen Bi,Hourong Cai,Shengjun Xue,Wei You,Bin Liu,Handong Jiang
出处
期刊:Respirology
[Wiley]
日期:2016-05-17
卷期号:21 (6): 1075-1080
被引量:39
摘要
Abstract Background and objective The roles of bile acid microaspiration and bile acid‐activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. Methods Human AECs and normal or IPF‐derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial‐mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR‐independent pathways in bile acid‐induced profibrotic effects were also investigated. Results LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α‐SMA and vimentin and decreased E‐cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid‐induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid‐stimulated A549 cells, which contained increased levels of profibrotic factors. TGF‐β/Smad3 signaling was also involved in the bile acid‐induced EMT and lung fibroblast differentiation. Conclusion Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR‐dependent and independent pathways.
科研通智能强力驱动
Strongly Powered by AbleSci AI