Hepatocyte Growth Factor in Tissue Regeneration and Anti-fibrosis
Division of Molecular Regenerative Medicine,
Hepatocyte growth factor (HGF) was originally identified as a mitogenic protein for mature hepatocytes. HGF exerts multiple biological actions involved in cell proliferation, migration, morphogenesis, and apoptosis, through the Met receptor tyrosine kinase. Physiologically, HGF plays roles in regeneration and protection of organs such as the liver and kidney. Administration of HGF or HGF gene therapy has potent therapeutic effects on various acute and chronic diseases in distinct organs. Particularly HGF induces recovery from sclerotic disorder, including liver cirrhosis and chronic renal disease. In case of liver cirrhosis, HGF suppresses expression of TGF-b, the most potent fibrogenic growth factor, enhances proteolysis of extracellular matrix, stimulates proliferation of hepatocytes, and these are associated with remarkable improvement of liver cirrhosis. Because HGF orchestrates different biological activities, depending on target cell types, the recovery from fibrotic diseases associated with irreversible pathology seems to be achieved. Clinical trials of HGF are ongoing.