A single administration of adenoviral-mediated HGF cDNA permits survival of mice from acute hepatic failure.
Heptatocyte growth factor (HGF) having a variety of biological activity was suggested as a protective agent against acute toxic hepatic injury or a potentially therapeutic agent. For the efficient in vivo application of this factor, we employed adenoviral-mediated HGF gene delivery system. In this study, we constructed E1-deleted recombinant adenovirus carrying cDNA of human HGF (Ad.hHGF) and elucidated that HGF was efficiently expressed in the liver of C57/BL mice. A mouse model of acute hepatic failure was induced by high dose (1000mg/kg) of thioacetamide (TA) administration. Mice infected with Ad.hHGF showed a dramatic resistance to TA-induced acute hepatic injury. Serum ALT was increased transiently and then the level was normalized in Ad.hHGF-infected mice with TA administration. Furthermore, the survival rate was remarkably enhanced in the mice infected with Ad.hHGF. In the histological examination, massive hepatic necrosis induced by TA was almost completely protected by HGF produced by Ad.hHGF. Our results indicate that a single dose of HGF-encoding adenoviral vector maintained liver function and prevented the progression of liver necrosis in a mouse model of acute hepatic failure.
Hwang
Tae-Ho
TH
Department of Pharmacology, Dong-A University College of Medicine and Institute of Medical Science, Dongdaesin-Dong, Seo-Ku, Busan 602-103, South Korea.
Yoon
Byung-Cheol
BC
Jeong
Jin-Sook
JS
Seo
Su-Yeong
SY
Lee
Hye-Jeong
HJ
D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D017114:Liver Failure, Acute / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013853:Thioacetamide / Q000633:toxicity
D018076:DNA, Complementary; D013853:Thioacetamide; D017228:Hepatocyte Growth Factor; D000410:Alanine Transaminase