Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic rats suppressing apoptosis of hepatocytes

Abstract

Liver failure after hepatic resection is still a critical issue in the treatment of hepatic tumors in patients with liver cirrhosis. In the current study, the effect of hepatocyte growth factor (HGF) gene transfer, which is a multipotent growth factor, was examined in rats with liver cirrhosis that underwent 2/3 partial hepatectomy (PH). Rats were treated with 1 mL of 1% dimethylnitrosoamine (DMN) 3 consecutive days per week for 4 weeks and then received a 2/3 PH. Three days before the PH, human HGF gene plasmid (20 microg) encapsulated in hemagglutinating virus of Japan (HVJ)-liposome was administered through a direct injection in the portal vein. Control cirrhotic rats received empty HVJ-liposome in the same manner. HGF gene transfer significantly improved survival after PH in the cirrhotic rats, and it stimulated BrdU uptake in hepatocytes. Although the HGF gene transfer did not change the liver regeneration rate after PH, it suppressed hepatocyte apoptosis and upregulated an antiapoptotic protein, Bcl-xl, but it did not affect the expression of Bax, which is a proapoptotic protein. HGF gene transfer to cirrhotic livers improves liver failure-associated death after PH upregulating expression of an antiapoptotic protein, Bcl-xl.