Hepatocyte growth factor suppresses the onset of liver cirrhosis and abrogates lethal hepatic dysfunction in rats.
Heptic fibrosis/cirrhosis is a common hepatic disease characterized by the hyper-accumulation of connective tissue components, and hepatic necrosis. Chronic alcohol ingestion, viral infection, and metabolic disorders are contributing factors and there has been no effective treatment. Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is a long-sought hepatotrophic factor for liver regeneration. Administration of human recombinant HGF into rats with hepatic fibrosis/cirrhosis caused by dimethylnitrosamine (DMN) elicited mitogenic action for hepatocytes, stimulated hepatic collagenase activity, and prevented the onset and progression of hepatic fibrosis/cirrhosis. Accumulation of fibrous tissue components in the liver due to DMN-treatment were markedly decreased in HGF-injected rats. Moreover, HGF completely abrogated death caused by severe hepatic cirrhosis and dysfunction. We postulate that HGF may prove to be an effective treatment for human liver fibrosis/cirrhosis and for chronic hepatic failure.
Matsuda
Y
Y
Department of Oncology, Osaka University Medical School.
Matsumoto
K
K
Ichida
T
T
Nakamura
T
T
D000818:Animals; D002908:Chronic Disease; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000627:therapeutic use*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017093:Liver Failure / Q000150:complications / Q000188:drug therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D017364:Collagenases; D004128:Dimethylnitrosamine