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Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo 被引量:26

Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo
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摘要 AIM:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) 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 α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, 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. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0, 458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis. AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosisin vitro and in vivo.METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) 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 α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-L, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected.RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ,, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group,the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0,458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L,respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13.CONCLUSION: All these results indicated that rAAV-INF-γhas potential effects for gene therapy of hepatic fibrosis,which could inhibit the progression of hepatic fibrosis.
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第26期4045-4051,共7页 世界胃肠病学杂志(英文版)
基金 Supported by the National High Technology Research and Development Program of China, 863 Program, No. 2003AA2Z347A
关键词 Adeno-associated virus Interferon-γ Hepatic stellate cells Hepatic fibrosis 病毒感染 干扰素-γ 肝纤维化 病理机制
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  • 1[1]Hui AY,Friedman SL.Molecular basis of hepatic fibrosis.Expert Rev Mol Med 2003; 2003:1-23
  • 2[2]Alcolado R,Arthur MJ,Iredale JP.Pathogenesis of liver fibrosis.Clin Sci 1997; 92:103-112
  • 3[3]Safadi R,Friedman SL.Hepatic fibrosis-role of hepatic stellate cell activation.Med Gen Med 2002; 4:27
  • 4[4]Gressner AM.Cytokines and cellular crosstalk involved in the activation of fat-storing cells.J Hepatol 1995; 22:28-36
  • 5[5]Friedman SL.Molecular mechanisms of hepatic fibrosis and principles of therapy.J Gastroenerol 1997; 32:424-430
  • 6[6]McGuire RF,Bissell DM,Boyles J,Roll FJ.Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver.Hepatology 1992; 15:989-997
  • 7[7]Schuppan D,Ruehl M,Somasundaram R,Hahn EG.Matrix as modulator of stellate cell and hepatic fibrogenesis.Semin Liver Dis 2001; 21:351-372
  • 8[8]Farrar MA,Schreiber RD.The molecular cell biology of interferon-gamma and its receptor.Annu Rev Immunol 1993; 11:571-611
  • 9[9]Shen H,Zhang M,Minuk GY,Gong Y.Different effects of rat interferon alpha,beta and gamma on rat hepatic stellate cell proliferation and activation.BMC Cell Biol 2002; 3:9
  • 10[10]Sakaida I,Uchida K,Matsumura Y,Okita K.Interferon gamma treatment prevents procollagen gene expression without affecting transforming growth factor-beta1 expression in pig serum-induced rat liver fibrosis in vivo.J Hepatol 1998;28:471-479

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