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Both of them inhibit <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 and Smad signalling and exhibit antifibrotic activity in the liver. However, little is known about the protective effects of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> against hepatitis c virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>)\u2010induced hepatic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Levels of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>, p\u2010<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> and fibrotic markers in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected human liver and in Huh\u20107.5 cells infected with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 2a (<jats:styled-content style=\"fixed-case\">JFH<\/jats:styled-content>\u20101) were investigated. The effect of adenovirus\u2010mediated overexpression of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> (Ad\u2010<jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activation via metformin and 5\u2010amino\u20101\u2010b\u2010D\u2010ribofuranosyl\u2010imidazole\u20104\u2010carboxamide (<jats:styled-content style=\"fixed-case\">AICAR<\/jats:styled-content>) on fibrotic gene expression was evaluated in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected cells. Finally, we examined the effect of Ad\u2010<jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activators on invasion and activation of <jats:styled-content style=\"fixed-case\">LX<\/jats:styled-content>2 human <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s induced by conditioned media from <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected hepatocyte (<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected human livers and Huh\u20107.5 cells infected with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> SHP mRNA<\/jats:styled-content> and protein levels were diminished compared with controls, whereas profibrotic factors were increased. Pharmacological <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activation recovered <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> expression, and Ad\u2010<jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> inhibited <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010induced fibrotic gene expression. This finding was accompanied by inhibition of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010stimulated nuclear factor\u2010kappa B, an inducer of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2. Moreover, CytoSelect invasion assay revealed that enhanced activity and invasiveness of hepatic stellate cells induced by <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that overexpression of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> and activation of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> reverses profibrogenic features of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected cells by decreasing <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 and fibrotic gene expression. These findings provide a rationale for <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> as a possible therapeutic target against <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010induced hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12871","type":"journal-article","created":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T11:36:51Z","timestamp":1431689811000},"page":"2233-2245","source":"Crossref","is-referenced-by-count":19,"title":["Small heterodimer partner attenuates profibrogenic features of hepatitis <scp>C<\/scp> virus\u2010infected cells"],"prefix":"10.1111","volume":"35","author":[{"given":"Gwon\u2010Soo","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Kyungpook National University School of Medicine Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Han","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of 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