Epidermal growth factor protects rat epithelial cells against acid-induceddamage through the activation of Na+/H+ exchangers

We examined the effect of epidermal growth factor (EGF) on acid-induced cel l damage in rat gastric epithelial cells (RGM1) and investigated the mechan isms of this effect. Cells were incubated with EGF for 5, 15, 30, and 60 mi n, and then immersed in an acidified medium (pH 4.0) for 30 min to induce c ell damage. EGF prevented cell damage in a concentration- and time-dependen t manner. EGF reduced the effects of the acidified medium on the cells, pre venting the reduction of intracellular pH. Replacement of Na+ with K+ in th e acidified medium canceled the effect of EGF. Indomethacin and W-7 (a Ca-c almodulin inhibitor) did not alter the protective effect of EGF. In contras t, genistein (a tyrosine kinase inhibitor), amiloride (a Na+/H+ exchangers I and II inhibitor). and wortmannin (a phosphatidylinositol 3-kinase inhibi tor) significantly decreased the effect of EGF. Expression of Na+/H+ exchan gers type I and type II was confirmed by reverse transcription-polymerase c hain reaction. Our results demonstrate that EGF prevents acid-induced cell damage, most likely through the activation of a Na+/H+ exchanger It via pho sphatidylinositol 3-kinase.