DC Field | Value | Language |
---|---|---|
dc.contributor.author | Sun, Rui | ko |
dc.contributor.author | Park, Ogyi | ko |
dc.contributor.author | Horiguchi, Norio | ko |
dc.contributor.author | Kulkarni, Shailin | ko |
dc.contributor.author | Jeong, Won-il | ko |
dc.contributor.author | Sun, Hao-Yu | ko |
dc.contributor.author | Radaeva, Svetlana | ko |
dc.contributor.author | Gao, Bin | ko |
dc.date.accessioned | 2010-04-06T08:48:15Z | - |
dc.date.available | 2010-04-06T08:48:15Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2006-10 | - |
dc.identifier.citation | HEPATOLOGY, v.44, no.4, pp.955 - 966 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10203/17566 | - |
dc.description.abstract | Increasing evidence suggests that liver regeneration is suppressed in patients with chronic HCV infection; however, the underlying mechanisms remain unclear. Previously, we demonstrated that injection of the synthetic double-stranded RNA (dsRNA) poly I:C to mimic viral infection suppresses liver regeneration in the partial hepatectomy (PHx) model, whereby IFN-gamma contributes to the inhibition. In this study, we examined the role of the IFN-gamma-activated downstream signal (STAT1) and genes (IRF-1, p21(cip1), and SOCS1) in liver regeneration and hepatocyte proliferation. Results show that disruption of the STAT1 gene abolished poly I:C suppression of liver regeneration and the inhibitory effect of poly I:C on liver regeneration was diminished in IRF-1(-/-) and p21(cip1-/-) mice. Treatment with IFN-gamma in vitro inhibited cell proliferation of wild-type mouse hepatocytes, but not STAT1(-/-) hepatocytes. The inhibitory effect of IFN-gamma on cell proliferation was also diminished in IRF-1(-/-) and p21(cip1-/-) hepatocytes, but enhanced in SOCS1(-/-) hepatocytes. Hepatocyte proliferation was unaffected by treatment with poly I:C alone, but when hepatocytes were co-cultured with liver lymphocytes, proliferation was inhibited by IFN-gamma/STAT1-dependent mechanisms. Moreover, in HCV-infected livers with cirrhosis, activation of STAT1 was detected and correlated positively with liver injury (elevated serum levels of AST) but negatively with hepatocyte proliferation (hepatocyte PCNA and Ki-67 positive immunostaining). In conclusion, STAT1 is involved in dsRNA suppression of liver regeneration; not only does STAT1 activation contribute to liver injury, it may also block liver repair through inhibition of hepatocyte proliferation in HCV-infected patients, playing an important role in the pathogenesis of disease. | - |
dc.language | English | - |
dc.language.iso | en_US | en |
dc.publisher | JOHN WILEY SONS INC | - |
dc.subject | CHRONIC HEPATITIS-C | - |
dc.subject | CYCLIN-DEPENDENT KINASE | - |
dc.subject | CELL-MEDIATED HEPATITIS | - |
dc.subject | VIRUS-INFECTION | - |
dc.subject | HEPATOCYTE PROLIFERATION | - |
dc.subject | INTERFERON-GAMMA | - |
dc.subject | PROGENITOR CELLS | - |
dc.subject | VIRAL-HEPATITIS | - |
dc.subject | MESSENGER-RNA | - |
dc.subject | UP-REGULATION | - |
dc.title | STAT1 contributes to dsRNA inhibition of liver regeneration after partial hepatectomy in mice | - |
dc.type | Article | - |
dc.identifier.wosid | 000241338200022 | - |
dc.identifier.scopusid | 2-s2.0-33750617477 | - |
dc.type.rims | ART | - |
dc.citation.volume | 44 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 955 | - |
dc.citation.endingpage | 966 | - |
dc.citation.publicationname | HEPATOLOGY | - |
dc.identifier.doi | 10.1002/hep.21344 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Jeong, Won-il | - |
dc.contributor.nonIdAuthor | Sun, Rui | - |
dc.contributor.nonIdAuthor | Park, Ogyi | - |
dc.contributor.nonIdAuthor | Horiguchi, Norio | - |
dc.contributor.nonIdAuthor | Kulkarni, Shailin | - |
dc.contributor.nonIdAuthor | Sun, Hao-Yu | - |
dc.contributor.nonIdAuthor | Radaeva, Svetlana | - |
dc.contributor.nonIdAuthor | Gao, Bin | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CHRONIC HEPATITIS-C | - |
dc.subject.keywordPlus | CYCLIN-DEPENDENT KINASE | - |
dc.subject.keywordPlus | CELL-MEDIATED HEPATITIS | - |
dc.subject.keywordPlus | VIRUS-INFECTION | - |
dc.subject.keywordPlus | HEPATOCYTE PROLIFERATION | - |
dc.subject.keywordPlus | INTERFERON-GAMMA | - |
dc.subject.keywordPlus | PROGENITOR CELLS | - |
dc.subject.keywordPlus | VIRAL-HEPATITIS | - |
dc.subject.keywordPlus | MESSENGER-RNA | - |
dc.subject.keywordPlus | UP-REGULATION | - |
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