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dc.contributor.author신윤용-
dc.contributor.author김대기-
dc.date.accessioned2019-11-19T16:30:49Z-
dc.date.available2019-11-19T16:30:49Z-
dc.date.issued2016-
dc.identifier.issn1015-8987-
dc.identifier.issn1421-9778-
dc.identifier.otherOAK-25853-
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/252016-
dc.description.abstractBackground/Aims: Hypoxia is an environmental factor that aggravates liver fibrosis. HIF1 alpha activates hepatic stellate cells (HSCs) and increases transforming growth factor-beta (TGF-beta) signaling and the epithelial mesenchymal transition (EMT), accelerating the progression of fibrosis. We evaluated the anti-fibrotic therapeutic potential of a small-molecule inhibitor of TGF-beta type I receptor kinase, EW-7197, on HIF1 alpha-derived TGF-beta signaling in cholestatic liver fibrosis. Methods: We used a bile duct ligation (BDL)-operated rat model to characterize the role of HIF1 alpha-derived TGF-beta signaling in liver fibrosis. Cellular assays were performed in LX-2 cells (human immortalized HSCs). The anti-fibrotic effects of EW-7197 in liver tissues and HSCs were investigated via biochemical assays, immunohistochemistry (IHC), immunofluorescence (IF), chromatin immunoprecipitation (ChIP) assays, real-time PCR, and western blotting. Results: In our BDL rat model, orally administered EW-7197 inhibited fibrosis and attenuated HIF1 alpha-induced activation of HSCs and EMT in vivo. In addition, EW-7197 inhibited HIF1 alpha-derived HS[activation and expression of EMT markers in LX-2 cells in vitro. Conclusion: This study suggests that FW-7197 exhibits potential as a treatment for liver fibrosis because it inhibits HIF1 alpha-induced TGF-beta signaling. (C) 2016 The Author(s) Published by S. Karger AG, Basel-
dc.languageEnglish-
dc.publisherKARGER-
dc.subjectCholestatic liver injury-
dc.subjectHepatic stellate cell-
dc.subjectTGF-beta-
dc.subjectHIF1 alpha-
dc.subjectEpithelial mesenchymal transition-
dc.subjectEW-7197-
dc.titleTGF-beta Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1 alpha-Induced Epithelial Mesenchymal Transition-
dc.typeArticle-
dc.relation.issue2-
dc.relation.volume38-
dc.relation.indexSCIE-
dc.relation.indexSCOPUS-
dc.relation.startpage571-
dc.relation.lastpage588-
dc.relation.journaltitleCELLULAR PHYSIOLOGY AND BIOCHEMISTRY-
dc.identifier.doi10.1159/000438651-
dc.identifier.wosidWOS:000371082300011-
dc.author.googleKim, Min-Jin-
dc.author.googlePark, Sang-A-
dc.author.googleKim, Chun Hwa-
dc.author.googlePark, So-Yeon-
dc.author.googleKim, Jung-Shin-
dc.author.googleKim, Dae-Kee-
dc.author.googleNam, Jeong-Seok-
dc.author.googleSheen, Yhun Yhong-
dc.contributor.scopusid신윤용(6603872711)-
dc.contributor.scopusid김대기(35083694200)-
dc.date.modifydate20210914114252-
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약학대학 > 약학과 > Journal papers
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