|Budget Amount *help
¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Hepatocyte growth factor(HGF)induces mitogenesis,motogenesis and morphogenesis of various epithelial cells,including mature hepatocytes and has been considered to act as a hepatotrophic factor for liver regeneration.We have studied induction of HGF following various injuries in the liver and kidney and identified inducers for HGF.Expression of HGF was rapidly and markedly induced following onset of various liver injuries(hepatitis,partial hepatectomy,etc.) or renal injuries(unilateral nephrectomy,ischemia,HgCl_2-administration,etc.)not only in injured organ but also in distant intact organs such as lung and spleen.Thus HGF seems to act as hepatotrophic and renotropic factor for regeneration of liver and kidney through a paracrine and an endorine mechanisms.We next found the presence of an inducer for expression of HGF in serum of rat with organ injury and named the factor "injurin".Injurin was partially purified from the serum of rats and was found to be acid-and heat-stable proteious factor with Mr of 10-30kDa.In addition to injurin,interleukin-1(IL-1)and heparin also increased HGF synthesis in cultured fibroblasts,whereas transforming growth factor-beta1(TGF-beta1)and glucocorticoids suppressed expression of HGF,acting as negative regulators for HGF.Injurin,IL-1,and heparin may be rapidly secreted following hepatic or renal injuries and induce expression of HGF.On the other hand TGF-beta1 may be involved in the termination of organ regeneration through its potential to suppress HGF expression.HGF and its regulators may have important roles not only for organ regeneration,but also for organogenesis and homeostasis of organs.