{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:01:30Z","timestamp":1790031690575,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81274143"],"award-info":[{"award-number":["81274143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>The roles of bile acid microaspiration and bile acid\u2010activated 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human AECs and normal or IPF\u2010derived 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\u2010mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR\u2010independent pathways in bile acid\u2010induced profibrotic effects were also investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u03b1\u2010SMA and vimentin and decreased E\u2010cadherin 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\u2010induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid\u2010stimulated A549 cells, which contained increased levels of profibrotic factors. TGF\u2010\u03b2\/Smad3 signaling was also involved in the bile acid\u2010induced EMT and lung fibroblast differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR\u2010dependent and independent pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/resp.12815","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T04:26:58Z","timestamp":1463459218000},"page":"1075-1080","source":"Crossref","is-referenced-by-count":56,"title":["Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor\u2010dependent and independent pathways"],"prefix":"10.1111","volume":"21","author":[{"given":"Bi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hou\u2010Rong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine the Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Jie","family":"You","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Dong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2009-040GL"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605669103"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62351-6"},{"key":"e_1_2_7_5_1","first-page":"213","article-title":"Epithelial cell alpha3beta1 integrin links beta\u2010catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis","volume":"119","author":"Kim KK","year":"2009","journal-title":"J. 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