Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo

To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-gamma for gene therapy in experimental hepatic fibrosis in vitro and in vivo. We constructed the recombinant AAV encoding human INF-gamma (rAAV- INF-gamma) and took the primary rat hepatic stellate cel...

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Published in:World journal of gastroenterology : WJG 2005-07, Vol.11 (26), p.4045-4051
Main Authors: Chen, Miao, Wang, Guang-Ji, Diao, Yong, Xu, Rui-An, Xie, Hai-Tang, Li, Xin-Yan, Sun, Jian-Guo
Format: Article
Language:English
Subjects:
Animals
Basic Research
Carbon Tetrachloride Poisoning - prevention & control
Cells, Cultured
Collagenases - genetics
Dependovirus - genetics
Dependovirus - immunology
Disease Models, Animal
Disease Progression
Humans
Interferon-gamma - pharmacology
Liver - cytology
Liver - drug effects
Liver - immunology
Liver Cirrhosis, Experimental - prevention & control
Liver Function Tests
Matrix Metalloproteinase 13
Rats
Recombinant Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Tissue Inhibitor of Metalloproteinase-1 - genetics
Transforming Growth Factor beta - genetics
Virion - immunology
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Summary:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-gamma for gene therapy in experimental hepatic fibrosis in vitro and in vivo. We constructed the recombinant AAV encoding human INF-gamma (rAAV- INF-gamma) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of alpha-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-beta, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. In vitro study, AAV vector could mediated efficient expression of human INF-gamma, which inhibit the activation of hepatic stellate cells, decrease the expression of alpha-SMA and mRNA of TIMP-1, TGF-beta, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-gamma could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-gamma induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177+/-28 microg/g wet liver, 668.5+/-140.0, 458.4+/-123.5 U/L, compare with the fibrosis control group 236+/-31 microg/g wet liver, 1 019.1+/-276.3, 770.5+/-154.3 U/L, respectively (P
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v11.i26.4045