HEPATOCYTE GROWTH-FACTOR IS THE MOST POTENT ENDOGENOUS STIMULANT OF RABBIT GASTRIC EPITHELIAL-CELL PROLIFERATION AND MIGRATION IN PRIMARY CULTURE

Various growth factors are suggested to be involved in gastric mucosal repair. Our previous studies have shown that exogenous hepatocyte gro wth factor (HGF) has a proliferative effect on gastric epithelial cell s, In the present study, comparison of the maximum proliferative effec ts and the optimum concentrations of several growth factors revealed t hat HGF was the most potent mitogen for gastric epithelial cells, as i s the case for hepatocytes, Restitution of gastric epithelial cell mon olayers was assessed using a round wound restitution model, HGF was th e most effective agent for facilitating gastric epithelial restitution among those tested. A binding assay revealed specific binding of HGF to its receptor on gastric epithelial cells. Northern blot analysis co nfirmed the expression of specific HGF receptor mRNA (c-met) by gastri c epithelial cells but not by gastric fibroblasts, To investigate endo genous HGF production, we determined the effect of gastric fibroblast- conditioned medium on epithelial proliferation and restitution, The co nditioned medium produced similar effects to HGF and its activity was neutralized by an anti-HGF antibody. In addition, expression of HGF mR NA was detected in gastric fibroblasts but not in gastric epithelial c ells. Our immunohistochemical study confirmed these in vitro data by m eans of demonstrating the existence and localization of HGF at human n ative gastric mucosa, HGF was localized at fibroblasts under the epith elial cell layer around gastric ulcers, These results suggest that HGF may be a potent endogenous promotor of gastric epithelial cell prolif eration and migration, and may contribute to gastric mucosal repair th rough a paracrine mechanism.