TGF-beta Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1 alpha-Induced Epithelial Mesenchymal Transition
DC Field | Value | Language |
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dc.contributor.author | Kim, Min-Jin | - |
dc.contributor.author | Park, Sang-A | - |
dc.contributor.author | Kim, Chun Hwa | - |
dc.contributor.author | Park, So-Yeon | - |
dc.contributor.author | Kim, Jung-Shin | - |
dc.contributor.author | Kim, Dae-Kee | - |
dc.contributor.author | Nam, Jeong-Seok | - |
dc.contributor.author | Sheen, Yhun Yhong | - |
dc.date.available | 2020-02-28T06:43:27Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1015-8987 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/9701 | - |
dc.description.abstract | Background/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.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | KARGER | - |
dc.relation.isPartOf | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | - |
dc.subject | HYPOXIA-INDUCIBLE FACTOR | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | HEPATIC STELLATE CELLS | - |
dc.subject | INTRINSIC MARKERS | - |
dc.subject | FIBROGENESIS | - |
dc.subject | ACTIVATION | - |
dc.subject | MECHANISMS | - |
dc.subject | EXPRESSION | - |
dc.subject | CANCER | - |
dc.subject | INFLAMMATION | - |
dc.title | TGF-beta Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1 alpha-Induced Epithelial Mesenchymal Transition | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000371082300011 | - |
dc.identifier.doi | 10.1159/000438651 | - |
dc.identifier.bibliographicCitation | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v.38, no.2, pp.571 - 588 | - |
dc.identifier.scopusid | 2-s2.0-84971595292 | - |
dc.citation.endPage | 588 | - |
dc.citation.startPage | 571 | - |
dc.citation.title | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | - |
dc.citation.volume | 38 | - |
dc.citation.number | 2 | - |
dc.contributor.affiliatedAuthor | Nam, Jeong-Seok | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Cholestatic liver injury | - |
dc.subject.keywordAuthor | Hepatic stellate cell | - |
dc.subject.keywordAuthor | TGF-beta | - |
dc.subject.keywordAuthor | HIF1 alpha | - |
dc.subject.keywordAuthor | Epithelial mesenchymal transition | - |
dc.subject.keywordAuthor | EW-7197 | - |
dc.subject.keywordPlus | HYPOXIA-INDUCIBLE FACTOR | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | HEPATIC STELLATE CELLS | - |
dc.subject.keywordPlus | INTRINSIC MARKERS | - |
dc.subject.keywordPlus | FIBROGENESIS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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