Document Detail

Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions.
MedLine Citation:
PMID:  1312869     Owner:  NLM     Status:  MEDLINE    
Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration.
K Matsumoto; T Nakamura
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Critical reviews in oncogenesis     Volume:  3     ISSN:  0893-9675     ISO Abbreviation:  Crit Rev Oncog     Publication Date:  1992  
Date Detail:
Created Date:  1992-04-24     Completed Date:  1992-04-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8914610     Medline TA:  Crit Rev Oncog     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  27-54     Citation Subset:  IM    
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Base Sequence
Cell Communication / physiology
Cell Division / physiology
Chromosome Mapping
Gene Expression Regulation
Growth Substances / chemistry,  isolation & purification,  physiology*
Hepatocyte Growth Factor
Kidney / pathology
Liver Regeneration / physiology*
Molecular Sequence Data
Molecular Structure
Platelet-Derived Growth Factor / physiology
Protein Precursors / genetics,  physiology
Proto-Oncogene Proteins c-met
Receptors, Cell Surface / physiology
Sequence Homology, Nucleic Acid
Transforming Growth Factor beta / genetics,  physiology
Reg. No./Substance:
0/Growth Substances; 0/Platelet-Derived Growth Factor; 0/Protein Precursors; 0/Receptors, Cell Surface; 0/Transforming Growth Factor beta; 67256-21-7/Hepatocyte Growth Factor; EC Proteins c-met

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