國家衛生研究院 NHRI:Item 3990099045/11393
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11393


    Title: AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage
    Authors: Fang, CC;Wu, CF;Liao, YJ;Huang, SF;Chen, M;Chen, YMA
    Contributors: National Mosquito-Borne Diseases Control Research Center;Institute of Molecular and Genomic Medicine
    Abstract: Glycine N-methyltransferase (GNMT) is abundantly expressed in normal livers and plays a protective role against tumor formation. 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 Gnmt−/− 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 (CCl4)-induced liver fibrosis in BALB/c mice. We showed that AAV8-GNMT protected hepatocytes from CCl4-induced liver damage. AAV8-GNMT significantly attenuated the levels of pro-fibrotic markers 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.
    Date: 2018-09-14
    Relation: Scientific Reports. 2018 Sep 14;8:Article number 13802.
    Link to: http://dx.doi.org/10.1038/s41598-018-30800-3
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000444571200010
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85053255022
    Appears in Collections:[Others] Periodical Articles
    [Shiu-Feng Kathy Huang] Periodical Articles

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