Effects of hepatocyte growth factor on rat inflammatory bowel disease models.

Hepatocyte growth factor (HGF) is a hepatotrophic factor and, also, functions as an epithelial growth factor. We examined the therapeutic effects of HGF on rat inflammatory bowel disease models induced by trinitrobenzensulfonic acid or dextran sulfate sodium. Recombinant human HGF was continuously administered at 50 microg/body/day using an intraperitoneally implanted pump for 7 days. Treatment of HGF reduced the ulcerated area, histological damage score, mucosal myeloperoxidase activity, and epithelial apoptotic rate but did not increase epithelial mitotic rate and immunohistochemical labeling indexes of proliferating cell nuclear antigen, Ki-67, and bromodeoxyuridine as indexes of epithelial cell proliferation in either model. We then examined the epithelial localization of the HGF receptor c-met and identified it on the surface epithelia, where apoptosis was observed, but did not find it in the proliferative zone. These results suggest that HGF exhibits therapeutic effects via anti-inflammation including antiapoptosis rather than epithelial cell proliferation in these inflammatory bowel disease models.