A novel STAT3 inhibitor, STX-0119, attenuates liver fibrosis by inactivating hepatic stellate cells in mice
DC Field | Value | Language |
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dc.contributor.author | Choi, Seungho | - |
dc.contributor.author | Jung, Hyun Jin | - |
dc.contributor.author | Kim, Min Woo | - |
dc.contributor.author | Kang, Ju-Hee | - |
dc.contributor.author | Shin, Dongyun | - |
dc.contributor.author | Jang, Yeong-Su | - |
dc.contributor.author | Yoon, Yeo Sung | - |
dc.contributor.author | Oh, Seung Hyun | - |
dc.date.available | 2020-02-27T03:41:04Z | - |
dc.date.created | 2020-02-04 | - |
dc.date.issued | 2019-05-21 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/1477 | - |
dc.description.abstract | Liver fibrosis is characterized by formation of scar tissue in the liver. The role of STAT3 signaling has been implicated on activating hepatic stellate cells (HSC) to myofibroblast-like cells in liver fibrosis. Major factors that activate STAT3 signaling are TGF-beta 1 and IL-6, which are upregulated in the liver in patients afflicted with liver fibrosis. Recent reports indicate that not only IL-6, but also the non-canonical signaling pathway of TGF-beta 1 is associated with STAT3 signaling. In this study, we demonstrate a new function of the STAT3 inhibitor, STX-0119, in liver fibrosis. STX-0119 is an inhibitor of STAT3 dimerization, which is required for nuclear localization of STAT3. We first investigated the anti-fibrotic effect of STX-0119 in in vitro experiments. Exposure to STX-0119 inhibited the nuclear localization of STAT3 in HSC5, resulting in decreased expression of its target genes, such as collal and alpha SMA. In addition, STX-0119 also inhibited the TGF-beta 1/1-6-induced activation of HSCs. Next, we examined the in vivo effect of STX-0119 in the liver fibrosis mouse model using thioacetamide (TAA) and carbon tetrachloride (CCL4). STX-0119 attenuated the TAA-induced liver fibrosis by inhibiting activation of HSC5 to myofibroblast-like cells. Consistent with the in vivo results using TAA-induced liver fibrosis model, treatment of STX-0119 similarly attenuated CCl4-induced liver fibrosis. In conclusion, we believe that STX-0119 inhibits the development of liver fibrosis by blocking the activation of hepatic stellate cells. These results indicate that STX-0119 is a potential new therapeutic strategy to prevent disease progression to cirrhosis. (C) 2019 Elsevier Inc. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.relation.isPartOf | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | TGF-BETA | - |
dc.subject | ACTIVATION | - |
dc.subject | PROLIFERATION | - |
dc.subject | INJURY | - |
dc.title | A novel STAT3 inhibitor, STX-0119, attenuates liver fibrosis by inactivating hepatic stellate cells in mice | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000468257300008 | - |
dc.identifier.doi | 10.1016/j.bbrc.2019.03.156 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.513, no.1, pp.49 - 55 | - |
dc.identifier.scopusid | 2-s2.0-85063485588 | - |
dc.citation.endPage | 55 | - |
dc.citation.startPage | 49 | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 513 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Kang, Ju-Hee | - |
dc.contributor.affiliatedAuthor | Shin, Dongyun | - |
dc.contributor.affiliatedAuthor | Jang, Yeong-Su | - |
dc.contributor.affiliatedAuthor | Oh, Seung Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Liver fibrosis | - |
dc.subject.keywordAuthor | Cirrhosis | - |
dc.subject.keywordAuthor | Hepatic stellate cell | - |
dc.subject.keywordAuthor | STAT3 | - |
dc.subject.keywordAuthor | STX-0119 | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | INJURY | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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