In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice: A comparative study to HGF

JOURNAL OF HEPATOLOGY

卷:44

Article

Khai, Ngin Cin ; Takahashi, Tornoyuki ; Ushikoshi, Hiroaki ; Nagano, Satoshi ; Yuge, Kentaro ; Esaki, Masayasu ; Kawai, Takao ; Goto, Kazuko ; Murofushi, Yoshiteru ; Fujiwara, Takako ; Fujiwara, Hisayoshi ; Kosai, Ken-ichiro

关键词: heparin-binding epidermal growth factor-like growth factor;    HB-EGF;    hepatocyte growth factor;    HGF;    growth factor;    gene therapy;    apoptosis;    fulminant hepatic failure;    Fas;    liver regeneration;    adenoviral vector;   

DOI  :  10.1016/j.jhep.2005.10.027

来源: Elsevier

【 摘 要 】

Background/Aims: It is unknown whether heparin-binding EGF-like growth factor (HB-EGF) can be a therapeutic agent, although previous studies suggested that HB-EGF might be a hepatotrophic factor. This study explores the potential of hepatic HB-EGF gene therapy in comparison with HGF. Methods: Mice received an intraperitoneal injection of the agonistic anti-Fas antibody 72 h after an intravenous injection of either adenoviral vector (1 X 10(11) particles) expressing human HB-EGF (Ad.HB-EGF), human HGF (Ad.HGF) or no gene (Ad.dE1.3), and were sacrificed 24 or 36 h later to assess liver injury and regeneration. Results: Exogenous HB-EGF was predominantly localized on the membrane, suggesting the initial synthesis of proHB-EGF in hepatocytes. The control Ad.dE1.3-treated mice represented remarkable increases in serum ALT and AST levels and histopathologically severe liver injuries with numerous apoptosis, but a limited number of mitogenic hepatocytes. In contrast, the liver injuries and apoptotic changes were significantly inhibited, but the mitogenic hepatocytes remarkably increased, in both the Ad.HB-EGF- and Ad.HGF-treated mice. More mitogenic hepatocytes and milder injuries were observed in the Ad.HB-EGF-treated mice. Conclusions: HB-EGF has more potent protective and mitogenic effects for hepatocytes than HGF, at least for the present conditions. In vivo hepatic HB-EGF gene transduction is therapeutic for Fas-induced liver injury. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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