Roles of HGF as a pleiotropic factor in organ regeneration.

Hepatocyte growth factor (HGF) has been discovered, purified, and molecularly cloned as a potent mitogen for mature hepatocytes. HGF is produced by mesenchymal cells and predominantly acts on a wide variety of epithelial cells, as a mitogen (stimulation of cell growth), a motogen (stimulation of cell motility), and a morphogen (induction of multicellular architecture). HGF mRNA and HGF protein are rapidly and markedly increased in the liver and plasma of rats with various types of liver injuries, and HGF receptors on plasma membranes of the liver were almost completely down-regulated due to HGF-binding and subsequent internalization. Thus HGF acts as a hepatotrophic factor for regeneration; intravenously injected recombinant HGF remarkably enhances liver regeneration. HGF mRNA, HGF protein, and HGF receptors in the kidney are also rapidly altered prior to the onset of renal tubular cell replication after various renal insults, thus HGF also acts as a renotropic factor in renal regeneration. HGF mRNA is rapidly induced not only in the injured organ but also in non-injured organs such as the lung and spleen following hepatic or renal injury. Because "injurin", a protenous factor which induces HGF mRNA expression, was detected in the plasma of rats with various organ injuries, it seems to increase HGF mRNA expression in non-injured organs and HGF produced in non-injured organs may also participate in the regeneration of the liver or kidney through an endocrine mechanism. Based on these results and its uniquely suited ability to act as mitogen, motogen and morphogen, HGF is considered to be a key molecule for construction of normal tissue structure during embryogenesis, organogenesis, and organ regeneration.