AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage

Cheng Chieh Fang, Ching Fen Wu, Yi Jen Liao, Shiu Feng Huang, Marcelo Chen, Yi Ming Arthur Chen

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number13802
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Glycine N-Methyltransferase
Dependovirus
Carbon Tetrachloride
Hepatocellular Carcinoma
Liver
Liver Cirrhosis
Genetic Therapy
Hepatocytes
Serogroup
Genes
Liver Diseases

ASJC Scopus subject areas

  • General

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AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage. / Fang, Cheng Chieh; Wu, Ching Fen; Liao, Yi Jen; Huang, Shiu Feng; Chen, Marcelo; Chen, Yi Ming Arthur.

In: Scientific Reports, Vol. 8, No. 1, 13802, 01.12.2018.

Research output: Contribution to journalArticle

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