Epidermal growth factor alters the bax : bcl-w ratio following massive small bowel resection

Background. Following massive small bowel resection (SBR), the expression o f bax and bcl-w is associated with increased enterocyte apoptosis. Epiderma l growth factor (EGF) has been shown to enhance enterocyte proliferation an d retard apoptosis in the adapting bowel. This study examined the effect of EGF on the expression of these bcl-2 family members during adaptation. Materials and methods. Mice (C57Bl/6; n = 38) underwent a 50% SBR or sham o peration and then were randomized to receive twice-daily orogastric saline or EGF (50 mu g/kg/day). After 3 days, the remnant ileum was removed, apopt otic index (No. apoptotic bodies/ crypt) calculated, and expression of mRNA and protein for bax and bcl-w quantified. Results. EGF prevented the expected increase in the apoptotic index after S BR and altered the ratio of bax to bcl-w in favor of cell survival. Conclusion. Following massive small bowel resection, EGF retards rates of e nterocyte apoptosis and modifies the expression of bcl-2 family members. By decreasing bax and increasing bcl-2 expression, the balance between pro- a nd anti-apoptotic genes is shifted in favor of cell survival. Alteration of bcl-2 family member expression may be an important mechanism by which EGF reduces the increased enterocyte apoptosis that occurs after massive small bowel resection. (C) 2000 Academic Press.