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In the present study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA). Repeated microaspiration of CDCA, DCA, and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial\u2013mesenchymal transition (EMT), as indicated by up-regulation of mesenchymal markers \u03b1-smooth muscle actin (\u03b1-SMA) and vimentin, as well as down-regulaton of epithelial markers E-cadherin and cytokeratin in alveolar epithelium of rat lungs. The expression of fibrogenic mediators, including transforming growth factor-\u03b21 (TGF-\u03b21), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and periostin, was significantly elevated in rat lungs exposed to microaspiration of bile acids. Furthermore, microaspiration of bile acids also induced p-Smad3 and farnesoid X receptor (FXR) expression in rat lungs. Our findings suggest that microaspiration of bile acids could promote the development of pulmonary fibrosis in\u00a0vivo, possibly via stimulating fibrogenic mediator expression and activating TGF-\u03b21\/Smad3 signaling and FXR.<\/jats:p>","DOI":"10.1042\/cs20160926","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T20:26:54Z","timestamp":1490387214000},"page":"951-963","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats"],"prefix":"10.1042","volume":"131","author":[{"given":"Bi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Department of Respiratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u00a0Jie","family":"You","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u00a0Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u00a0Dong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2017,5,4]]},"reference":[{"key":"2021113010502194000_B1","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1183\/09031936.00073012","article-title":"The pathogenesis of pulmonary fibrosis: a moving target","volume":"41","author":"Wuyts","year":"2013","journal-title":"Eur. 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