DC Field | Value | Language |
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dc.contributor.author | Jung, Gwon-Soo | ko |
dc.contributor.author | Jeon, Jae-Han | ko |
dc.contributor.author | Choi, Yeon-Kyung | ko |
dc.contributor.author | Jang, Se Young | ko |
dc.contributor.author | Park, Soo Young | ko |
dc.contributor.author | Kim, Mi-Kyung | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Jeong, Won-Il | ko |
dc.contributor.author | Lee, In-Kyu | ko |
dc.contributor.author | Kang, Yu Na | ko |
dc.contributor.author | Park, Keun-Gyu | ko |
dc.date.accessioned | 2016-04-12T08:36:45Z | - |
dc.date.available | 2016-04-12T08:36:45Z | - |
dc.date.created | 2015-10-29 | - |
dc.date.created | 2015-10-29 | - |
dc.date.issued | 2015-10 | - |
dc.identifier.citation | LIVER INTERNATIONAL, v.35, no.10, pp.2233 - 2245 | - |
dc.identifier.issn | 1478-3223 | - |
dc.identifier.uri | http://hdl.handle.net/10203/203657 | - |
dc.description.abstract | Background & AimsAn atypical orphan nuclear receptor small heterodimer partner (SHP) is known to be regulated by AMP-activated protein kinase (AMPK). Both of them inhibit TGF- and Smad signalling and exhibit antifibrotic activity in the liver. However, little is known about the protective effects of SHP and AMPK against hepatitis c virus (HCV)-induced hepatic fibrosis. MethodsLevels of SHP, p-AMPK and fibrotic markers in HCV-infected human liver and in Huh-7.5 cells infected with HCV genotype 2a (JFH-1) were investigated. The effect of adenovirus-mediated overexpression of SHP (Ad-SHP) and AMPK activation via metformin and 5-amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) on fibrotic gene expression was evaluated in HCV-infected cells. Finally, we examined the effect of Ad-SHP and AMPK activators on invasion and activation of LX2 human HSCs induced by conditioned media from HCV-infected hepatocyte (CM). ResultsIn HCV-infected human livers and Huh-7.5 cells infected with HCV, SHP mRNA and protein levels were diminished compared with controls, whereas profibrotic factors were increased. Pharmacological AMPK activation recovered SHP expression, and Ad-SHP inhibited HCV-induced fibrotic gene expression. This finding was accompanied by inhibition of HCV-stimulated nuclear factor-kappa B, an inducer of TGF-. Moreover, CytoSelect invasion assay revealed that enhanced activity and invasiveness of hepatic stellate cells induced by CM. ConclusionThese results demonstrate that overexpression of SHP and activation of AMPK reverses profibrogenic features of HCV-infected cells by decreasing TGF- and fibrotic gene expression. These findings provide a rationale for SHP as a possible therapeutic target against HCV-induced hepatic fibrosis. | - |
dc.language | English | - |
dc.publisher | WILEY-BLACKWELL | - |
dc.subject | NUCLEAR RECEPTOR SHP | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | STELLATE CELLS | - |
dc.subject | LIVER FIBROSIS | - |
dc.subject | TGF-BETA | - |
dc.subject | NATURAL-HISTORY | - |
dc.subject | METFORMIN | - |
dc.subject | INDUCTION | - |
dc.subject | GLUCONEOGENESIS | - |
dc.subject | TRANSACTIVATION | - |
dc.title | Small heterodimer partner attenuates profibrogenic features of hepatitis C virus-infected cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000362201800005 | - |
dc.identifier.scopusid | 2-s2.0-84942372052 | - |
dc.type.rims | ART | - |
dc.citation.volume | 35 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 2233 | - |
dc.citation.endingpage | 2245 | - |
dc.citation.publicationname | LIVER INTERNATIONAL | - |
dc.identifier.doi | 10.1111/liv.12871 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.localauthor | Jeong, Won-Il | - |
dc.contributor.nonIdAuthor | Jung, Gwon-Soo | - |
dc.contributor.nonIdAuthor | Jeon, Jae-Han | - |
dc.contributor.nonIdAuthor | Choi, Yeon-Kyung | - |
dc.contributor.nonIdAuthor | Jang, Se Young | - |
dc.contributor.nonIdAuthor | Park, Soo Young | - |
dc.contributor.nonIdAuthor | Kim, Mi-Kyung | - |
dc.contributor.nonIdAuthor | Lee, In-Kyu | - |
dc.contributor.nonIdAuthor | Kang, Yu Na | - |
dc.contributor.nonIdAuthor | Park, Keun-Gyu | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | AMP-activated protein kinase | - |
dc.subject.keywordAuthor | hepatitis C virus | - |
dc.subject.keywordAuthor | liver fibrosis | - |
dc.subject.keywordAuthor | small heterodimer partner | - |
dc.subject.keywordPlus | NUCLEAR RECEPTOR SHP | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | STELLATE CELLS | - |
dc.subject.keywordPlus | LIVER FIBROSIS | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | NATURAL-HISTORY | - |
dc.subject.keywordPlus | METFORMIN | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | GLUCONEOGENESIS | - |
dc.subject.keywordPlus | TRANSACTIVATION | - |
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