Hepatocyte growth factor: a regenerative drug for acute hepatitis and liver cirrhosis.
Liver cirrhosis is a major cause of morbidity worldwide and is characterized by the loss of hepatocytes with interstitial fibrosis. In this review, we discuss the potential uses of hepatocyte growth factor for treating hepatic diseases, focusing on the molecular mechanisms whereby hepatocyte growth factor reverses liver cirrhosis. Hepatic myofibroblasts play a central role in the development of liver cirrhosis, while myofibroblasts acquire c-Met. Using a rat model of liver cirrhosis, we recently delineated the direct effect of hepatocyte growth factor toward myofibroblasts: the induction of apoptotic cell death associated with matrix degradation, the inhibition of overproliferation and the suppression of transforming growth factor-beta1 production in myofibroblasts. Hepatocyte growth factor elicits mitogenic, anti-apoptotic and anti-inflammatory functions in hepatocytes, therefore contributing to reversing liver dysfunction. Considering the insufficient production of hepatocyte growth factor is responsible for the manifestation of chronic hepatitis, supplementation with or reinduction of hepatocyte growth factor represents a new strategy for attenuating intractable liver diseases.
Mizuno
Shinya
S
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
Nakamura
Toshikazu
T
D000208:Acute Disease; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000150:complications; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000502:physiology / Q000627:therapeutic use*; D022781:Hepatocytes / Q000473:pathology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met