Structure and function of hepatocyte growth factor.

Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes in primary culture, was first found in sera of partial hepatectomized rats and seems to be a hepatotrophic factor for liver regeneration which has not been purified over the past 30 years. HGF is composed of the 69 kDa alpha-subunit and the 34 kDa beta-subunit. Molecular cloning reveals that HGF is derived from a single chain precursor of 728 amino acid residues and it contains 4 kringle domains in the alpha-subunit. HGF gene spans about 70kb and consists of 18 exons and 17 introns. HGF is now thought to be a pleiotropic factor influencing a cell growth and cell motility for various epithelial cells. HGF receptor with Kd = 20-30pm is widely distributed in various epithelial cells including hepatocytes. HGF mRNA and HGF activity increase markedly in liver after various liver injuries and in kidney following unilateral nephrectomy or acute renal injury. Moreover, HGF mRNA is induced even in the intact lung in response to liver and kidney injury. In situ hybridization reveals that HGF-producing cells are mesenchymal cells such as Kupffer cells and sinusoidal endothelial cells in liver, fenestrated endothelial cells in kidney, and macrophages and endothelial cells in lung. Thus, HGF may play an important role as a paracrine or endocrine mediator through an epithelial-mesenchymal interaction in wound-healing, tissue or organ regeneration, morphogenesis and carcinogenesis.