In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice: a comparative study to HGF
| Autor: | Takao Kawai, Takako Fujiwara, Kazuko Goto, Ngin Cin Khai, Ken-ichiro Kosai, Satoshi Nagano, Hisayoshi Fujiwara, Kentaro Yuge, Masayasu Esaki, Tomoyuki Takahashi, Hiroaki Ushikoshi, Yoshiteru Murofushi |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Heparin-binding EGF-like growth factor medicine.medical_treatment Intraperitoneal injection Apoptosis Biology Antibodies Adenoviridae Mice In vivo Epidermal growth factor Transduction Genetic Internal medicine medicine Animals fas Receptor Liver injury Hepatology Epidermal Growth Factor Hepatocyte Growth Factor Growth factor Liver Diseases Cell Membrane Genetic Therapy medicine.disease Liver regeneration Liver Regeneration Mice Inbred C57BL Endocrinology Liver Cancer research Intercellular Signaling Peptides and Proteins Hepatocyte growth factor hormones hormone substitutes and hormone antagonists medicine.drug Heparin-binding EGF-like Growth Factor |
| Zdroj: | Journal of hepatology. 44(6) |
| ISSN: | 0168-8278 |
| Popis: | 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 72h after an intravenous injection of either adenoviral vector (1×10 11 particles) expressing human HB-EGF (Ad.HB-EGF), human HGF (Ad.HGF) or no gene (Ad.dE1.3), and were sacrificed 24 or 36h 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. |
| Databáze: | OpenAIRE |
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