HB-EGF/HGF Hepatic Gene Therapy Effectively Inhibits Bile Duct Ligated Cholestatic Liver Injury in Mice in Their Different Therapeutic Modes

• Published in: Molecular therapy Vol. 19; no. 7; p. 1379
• Main Authors: Kosai, Ken-ichiro, Sakamoto, Kouichi, Khai, Nign Cin, Wang, Yuqing, Maezono, Rie, Tanoue, Kiyonori, Takamatsu, Hideo, Matsufuji, Hiroshi
• Format: Journal Article
• Language: English
• Published: 01.07.2011
• ISSN: 1525-0016; 1525-0024

We previously demonstrated that heparin-binding EGF-like growth factor (HB-EGF) gene therapy inhibited fluminant hepatic failure in mice, and that HB-EGF had more potent protective and mitogenic effects for hepatocytes than hepatocyte growth factor (HGF), the well-studied hepatotrophic factor, in this model (NC Khai et al. J Hepatol 2006). This is the first study to explore the therapeutic effects and characteristics of HB-EGF alone, HGF alone and both combination gene therapy for preventing bile duct ligated cholestatic liver injury and fibrosis. In conclusion, hepatic gene therapy using HB-EGF and/or HGF significantly attenuated liver injuries, including hepatocyte deaths, cholestatis and liver fibrosis and induced liver regeneration at both acute and chronic stages. Interestingly, HB-EGF and HGF exerted therapeutic effects more predominantly at the acute and the chronic stages, respectively, and combination HG-EGF/HGF gene therapy may be attractive therapy for efficiently treating liver diseases on their different therapeutic modes.