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GNMT depletion leads to progression of hepatocellular carcinoma (HCC). In this study, we investigated the activity of ectopic GNMT delivered using recombinant adeno-associated virus (AAV) gene therapy in mouse models of liver cirrhosis and HCC. Injection of AAV serotype 8 (AAV8) vector carrying the GNMT gene (AAV8-GNMT) in\n                    <jats:italic>Gnmt<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice increased GNMT expression and downregulated pro-inflammatory responses, resulting in reduced liver damage and incidence of liver tumors. Moreover, AAV8-GNMT resulted in the amelioration of carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )-induced liver fibrosis in BALB\/c mice. We showed that AAV8-GNMT\u00a0protected hepatocytes from CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced liver damage.\u00a0 AAV8-GNMT\u00a0significantly attenuated the levels of\u00a0pro-fibrotic\u00a0markers and increased efficiency of hepatocyte proliferation. These results suggest that correction of hepatic GNMT by gene therapy of AAV8-mediated gene enhancement may provide a potential strategy for preventing and delaying development of liver diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-30800-3","type":"journal-article","created":{"date-parts":[[2018,9,10]],"date-time":"2018-09-10T05:13:52Z","timestamp":1536556432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage"],"prefix":"10.1038","volume":"8","author":[{"given":"Cheng-Chieh","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Fen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiu-Feng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-4964","authenticated-orcid":false,"given":"Yi-Ming Arthur","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"30800_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/978-3-0348-0837-8_16","volume":"816","author":"A Bishayee","year":"2014","unstructured":"Bishayee, A. 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