HEPATOCYTE GROWTH-FACTOR AND C-MET EXPRESSION IN LONG-EVANS CINNAMON RATS WITH SPONTANEOUS HEPATITIS AND HEPATOMA

The Long-Evans Cinnamon (LEG) rat is characterized by the spontaneous onset of acute and chronic hepatitis, followed by occurrence of liver cancer, and is thus able to provide a unique experimental model for hu man genetical liver disease, Wilson's disease, Hepatocyte growth facto r (HGF) is a potent hepatotrophic factor in liver regeneration, and it s expression is up-regulated in response to liver injuries, We found t hat the plasma HGF level in LEC rats rose markedly during the fulminan t hepatitis phase, fell during the phase of chronic/cholangiofibrosis, and fluctuated during the hepatoma phase, Immunohistological staining of the liver revealed that the number of HGF-positive cells increased remarkably during the fulminant hepatitis phase, and that many of the se cells were localized at the portal triads. Fewer HGF-positive cells were observed during the phase of chronic hepatitis, The surface of t he hepatocellular carcinoma (HCC) cells and the cytoplasm of the nonep ithelial cells in cancerous Liver tissues were HGF-positive. The HGF-m essenger RNA (mRNA) level in the liver rose in the fulminant hepatitis phase, fell in the chronic hepatitis phase, and was intermediate or h igh during the hepatoma phase. The expression of c-met mRNA was strong in the tissues of LEC rats with fulminant hepatitis and, especially, in the cholangiofibrosis tissues, c-met mRNA was also detected in HCCs , These results suggest that the HGF-c-met system may play an importan t role in the regeneration of hepatocytes as well as in the developmen t of HCC in paracrine or autocrine mechanisms.