Heparin-binding EGF-like growth factor is an autocrine growth factor for rat gastric epithelial cells.

We examined the biological action and expression of heparin-binding EGF-like growth factor (HB-EGF) in a rat gastric mucosal cell line, RGM1. HB-EGF stimulated DNA synthesis of RGM1 cells in a dose-dependent manner. Mitogenic effect of HB-EGF was as potent as that of other known mitogens for gastric epithelial cells, such as hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha. Northern blot analysis showed that RGM1 cells as well as rat gastric mucosal tissue expressed a 2.5-kilobase transcript of HB-EGF. Not only HB-EGF and TGF-alpha but also HGF caused a rapid induction of HB-EGF mRNA in the cells. Treatment with heparitinase which destroys heparan sulfate proteoglycan (HSPG) or with chlorate which inhibits sulfation of HSPG diminished [3H]thymidine incorporation of RGM1 cells in serum-free medium. In addition, a synthetic peptide corresponding to the heparin-binding domain of HB-EGF inhibits the DNA synthesis of RGM1 cells in serum-free medium in a dose-dependent manner. These results suggest that HB-EGF is an autocrine and paracrine growth factor for gastric epithelial cells and may play significant roles in mucosal repair of the stomach in cooperation with other growth factors.