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This study investigated the effects of simvastatin on the lipopolysaccharide (LPS)\u2010induced EMT and related signal pathways in BECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Biliary epithelial cells were exposed to LPS (2\u2009\u00b5g\/mL) or transforming growth factor \u03b21 (TGF\u2010\u03b21) (5\u2009ng\/mL) for 5\u2009days. The EMT was assessed by a gain of mesenchymal cell markers (vimentin, N\u2010cadherin, slug, and Twist\u20101) and a loss of epithelial cell markers (E\u2010cadherin). The effects of simvastatin on the EMT induced by LPS or TGF\u2010\u03b21 were determined by the changes in the levels of EMT markers and TLR4 and in the c\u2010Jun N\u2010terminal kinase (JNK), p38, and nuclear factor\u2010\u03baB (NF\u2010\u03baB) signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Compared with the BECs treated with LPS alone, co\u2010treatment with simvastatin and LPS induced an increase in the expression of E\u2010cadherin and decreases in the expression levels of mesenchymal cell markers. The LPS\u2010induced TLR4 expression level was slightly decreased by co\u2010treatment with simvastatin. LPS\u2010induced BEC growth was markedly inhibited by co\u2010treatment with simvastatin. Furthermore, pretreatment with simvastatin inhibited the LPS\u2010induced EMT in BECs by downregulating NF\u2010\u03baB and JNK phosphorylation. The suppressive effects of simvastatin pretreatment on the induction of the EMT by TGF\u2010\u03b21 were also demonstrated in H69 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Our results demonstrate that LPS or TGF\u2010\u03b21 promote the EMT in BECs that that pretreatment with simvastatin inhibited the induced EMT by downregulating toll\u2010like receptor 4 and NF\u2010\u03baB phosphorylation. This finding suggests that simvastatin can be considered a new agent for preventing biliary fibrosis associated with the EMT of BECs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13230","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T10:36:46Z","timestamp":1447756606000},"page":"1220-1228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Statin pretreatment inhibits the lipopolysaccharide\u2010induced epithelial\u2010mesenchymal transition via the downregulation of toll\u2010like receptor 4 and nuclear factor\u2010\u03baB in human biliary epithelial cells"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1536-116X","authenticated-orcid":false,"given":"Yangmi","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of Physiology Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jeoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Kyung","family":"Jang","sequence":"additional","affiliation":[{"name":"Departments of Physiology Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae\u2010Ghon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine Chonbuk National University  Jeonju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joung\u2010Ho","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chungbuk National University College of Medicine  Chungbuk Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl.2012.6.3.295"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294744"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20130"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/S0025-6196(11)63624-0","article-title":"Ludwig symposium on biliary disorders \u2013 part I. 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