Hepatocyte growth factor stimulates epithelial restitution in rabbit duodenum in vitro

Summary BACKGROUND: Hepatocyte growth factor (HGF) promotes healing of mechanically wounded intestinal epithelial-cell monolayers in vitro. Since the role of HGF for repair in native intestinal mucosa is not known, we investigated the effect of HGF on the restitution of rabbit duodena in vitro. METHODS: Following luminal administration of 10 mM HCl for 10 min, Ussing-chambered rabbit duodenal mucosa was incubated in luminal or serosal presence or absence (controls) of 20–200 ng of HGF per ml and/or tyrosine kinase inhibitor genistein (10 –6 M) for 3 h. Damage and repair were assessed by electrophysiology, histology, and morphometry. RESULTS: Luminal HCl decreased resistance by 60% and damaged 58% ± 5% of the mucosal surface (P < 0.01). Postinjury administration of serosal HGF (20–200 ng/ml) for 3 h induced dose-dependent resistance recovery and reduced acid-induced mucosal damage. Genistein completely blocked HGF-induced effects. Light microscopy showed that HGF accelerated the restitution of rabbit duodena in vitro by stimulation of enterocyte migration. CONCLUSIONS: Our results indicate that HGF is important in the maintenance of duodenal epithelial barrier integrity.