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


METHODS
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.


RESULTS
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.


CONCLUSIONS
HGF gene transfer to cirrhotic livers improves liver failure-associated death after PH upregulating expression of an antiapoptotic protein, Bcl-xl.
Nishino
Masayuki
M
Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Iimuro
Yuji
Y
Ueki
Takahiro
T
Hirano
Tadamichi
T
Fujimoto
Jiro
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006498:Hepatectomy / Q000401:mortality; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000601:surgery*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051020:bcl-X Protein / Q000096:biosynthesis
C494813:Bcl2l1 protein, rat; D051020:bcl-X Protein; D017228:Hepatocyte Growth Factor