mal accumulation of copper in the liver of LEC rats, 40 times The Long-Evans Cinnamon (LEC) rat is characterized greater than that in control Long-Evans Agouti rats, whereas by the spontaneous onset of acute and chronic hepatitis, the levels of ceruloplasmin in LEC rat serum were markedly followed by occurrence of liver cancer, and is thus able low. [4][5] It is worth noting that these features of the liver disorto provide a unique experimental model for human geder in LEC rats are very similar to those that characterize netical liver disease, Wilson's disease. HepatocyteWilson's disease. [4][5][6][7] Recently, Wu et al. 8 cloned complemengrowth factor (HGF) is a potent hepatotrophic factor in tary DNAs for a rat gene (Atp7b) homologous to the human liver regeneration, and its expression is up-regulated inWilson's disease gene (ATP7B) and identified a partial deleresponse to liver injuries. We found that the plasma HGF tion in the Atp7b gene in the LEC rat. level in LEC rats rose markedly during the fulminant Hepatocyte growth factor (HGF) was first identified in the hepatitis phase, fell during the phase of chronic/cholanserum of partially hepatectomized rats 9 and purified from rat giofibrosis, and fluctuated during the hepatoma phase.platelets 10 and human plasma. 11,12 HGF is a ligand for the cImmunohistological staining of the liver revealed that met protooncogene product of receptor-type tyrosine kinase, 13-17 the number of HGF-positive cells increased remarkably and is considered to be a major hepatotrophic factor in the during the fulminant hepatitis phase, and that many of induction of mitosis of hepatocytes during liver regenerathese cells were localized at the portal triads. Fewer tion. [18][19][20] Acting as a motogen, HGF induces cell move-HGF-positive cells were observed during the phase of ment, 21,22 and, while acting as a morphogen, it induces the chronic hepatitis. The surface of the hepatocellular carformation of tissue-like structures [23][24][25] for various cell types.
cinoma (HCC) cells and the cytoplasm of the nonepithe-The serum levels of HGF are elevated not only in human lial cells in cancerous liver tissues were HGF-positive.patients with fulminant hepatitis, but also in those with The HGF-messenger RNA (mRNA) level in the liver rose chronic hepatitis and cirrhosis. 26 HGF messenger RNA in the fulminant hepatitis phase, fell in the chronic hepa-(mRNA) is expressed in various tissues. 27 It has already been titis phase, and was intermediate or high during the hepreported that HGF production increases in rats injured by atoma phase. The expression of c-met mRNA was strong hepatectomy or CCl 4 , and that nonparenchymal cells produce in the tissues of LEC rats with fulminant hepatitis and, Both the levels of HGF mRNA and the activity of especially, in the cholangiofibrosis tissues. c-met mRNA HGF increase prior to liver regeneration. 28 It has also been was also detected in HCCs. These results suggest that reported that recombinant HGF has promoted remarkable the HGF-c-met system may pla...