Adenovirus-Mediated Hepatocyte Growth Factor Gene Transfer Prevents Lethal Liver Failure in Rats

• Published in: Biochemical and biophysical research communications 2000-11, Vol.278 (2), p.338-343
• Main Authors: Nomi, Takahiro, Shiota, Goshi, Isono, Masato, Sato, Kenzo, Kawasaki, Hironaka
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Alanine Transaminase - blood; Animals; antiapoptotic effect; Base Sequence; Bcl-xL; Bcl-xL protein; Caspase 3; Caspases - genetics; Cox-2; Cox-2 protein; cyclooxygenase; DNA Primers; galactosamine; gene transfer; Gene Transfer Techniques; hepatocyte growth factor; Hepatocyte Growth Factor - genetics; lipopolysaccharides; liver failure; Liver Failure - therapy; Male; Rats; Rats, Inbred F344; RNA, Messenger - genetics; Transfection
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3793

Hepatocyte growth factor (HGF) has a potent antiapoptotic effect on hepatocytes in d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-treated rats. Here, we report that adenovirus mediated HGF gene transfer into liver prevents liver failure and reduces mortality of rats treated with d-GalN/LPS. Fisher 344 rats, which were given intraperitoneal injections of pAxCAHGF 48 h before, were treated with d-GalN/LPS. Serum ALT in the HGF group at 6 and 12 h after d-GalN/LPS was decreased to 1/6 and 1/12 of the control group (P < 0.01, each). Concomitant reduction of apoptotic cells were also observed. The Kaplan–Meier analysis showed that a survival rate in the HGF group was improved, compared to that in the control group (P < 0.05). Caspase-3 activity in the HGF group decreased, compared to that in the control group, especially at 12 h (P < 0.05), although it maintained a high level in the control group. Expression of Bcl-xL and cyclooxygenase-2 (Cox-2) was induced in liver by HGF gene transfer. These data suggest that HGF exerts an antiapoptotic effect through dual induction of Bcl-xL and Cox-2, which suppresses caspase-3 activity.