{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:16:41Z","timestamp":1768810601358,"version":"3.49.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,2,28]],"date-time":"2006-02-28T00:00:00Z","timestamp":1141084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies are lacking. We have previously demonstrated that \u03b1\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010MSH) gene therapy protects against thioacetamide\u2010induced acute liver failure in mice. Recent reports showed that collagen metabolism is a novel target of \u03b1\u2010MSH. Therefore, the aim of this study is to investigate whether \u03b1\u2010MSH gene therapy possesses anti\u2010hepatic fibrogenic effect in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver fibrosis was induced in mice by administering carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) continuously for 10 weeks. \u03b1\u2010MSH expression plasmid was delivered via electroporation after liver fibrosis had been established. Histopathology, reverse\u2010transcription polymerase chain reaction (RT\u2010PCR), immunoblotting, and gelatin zymography were used to investigate its possible mechanisms of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u03b1\u2010MSH gene therapy reversed established liver fibrosis in CCl<jats:sub>4<\/jats:sub>\u2010treated mice. RT\u2010PCR revealed that \u03b1\u2010MSH gene therapy attenuated the liver TGF\u2010\u03b21, collagen \u03b11, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and cyclooxygenase\u20102 (COX\u20102) was significantly attenuated. Further, \u03b1\u2010MSH significantly increased matrix metalloproteinase (MMP) activity with tissue inhibitors of matrix metalloproteinase (TIMP) inactivation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have demonstrated that \u03b1\u2010MSH gene therapy reversed established liver fibrosis in mice. It also prevented the upregulated fibrogenic and proinflammatory gene response after CCl<jats:sub>4<\/jats:sub>administration. Its collagenolytic effect may be attributed to MMP and TIMP modulation. In summary, \u03b1\u2010MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.899","type":"journal-article","created":{"date-parts":[[2006,2,28]],"date-time":"2006-02-28T14:21:05Z","timestamp":1141136465000},"page":"764-772","source":"Crossref","is-referenced-by-count":26,"title":["\u03b1\u2010Melanocyte\u2010stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in 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