Production and activation of hepatocyte growth factor during the healing of rat gastric ulcers

The hepatocyte growth factor has been reported to be a potent mitogen of various epithelial cells, including gastric mucosal cells. Therefore, production and activation of hepatocyte growth factor in the gastric wall were investigated to speculate on the possible role of this factor in the healing of gastric ulcer in rats. Indomethacin-induced gastric mucosal lesions and acetic acid induced ulcers were employed as models of acute gastric lesions and chronic ulcer, respectively. Immunoblot and Northern blot analyses indicate that experimentally induced gastric mucosal lesions stimulate not only the production of hepatocyte growth factor, but also the conversion to its active form. This conversion was accompanied by increased gene expression of hepatocyte growth factor activator in the stomach. In rats with acute mucosal lesions, hepatocyte growth factor activator mRNA was most abundant 6 h after induction of mucosal lesions. On the other hand, hepatocyte growth factor and hepatocyte growth factor activator mRNA levels were elevated until 15 days after the induction of chronic ulcers. In summary, it has been clarified that not only production, but also activation of hepatocyte growth factor is stimulated during gastric ulcer healing.