THE EGF-BACKSLASH-EGF-RECEPTOR AXIS MODULATES ENTEROCYTE APOPTOSIS DURING INTESTINAL ADAPTATION

Background. Adaptation after small bowel resection (SBR) is characteri zed by a new set point in the balance of enterocyte proliferation and apoptosis. Since epidermal growth factor (EGF) augments both prolifera tion and adaptation, we sought to determine the effect of EGF receptor manipulation on apoptosis following SBR. Materials and Methods. Male ICR mice underwent 50% SBR or sham operation (bowel transection with r eanastomosis) and then were given EGF (50 mu g/kg/day) or saline by or ogastric gavage. At 1 week, a proliferation index (PI) was measured in the ileum by BrdU uptake and an apoptosis index in crypts (cAI) and v illi (vAI) scored by counting apoptotic bodies in enterocytes. In othe r experiments, AI was scored after SBR in mice with defective receptor s (waved-2). Results are expressed as means +/- SE and evaluated stati stically using ANOVA. # denotes P < 0.001. Results. Following SBR, EGF increased PI (40 +/- 2% vs 50 +/- 1% BrdU + cells; #), villus height (252 +/- 4 mu m vs 401 +/- 15 mu m; #), and crypt depth (77.3 +/- 1.5 mu m vs 120.8 +/- 5 mu m; #). When compared with sham, SBR resulted in increased cAI (0.3 +/- 0.02 vs 2.0 +/- 0.1; #) and vAI (0.4 +/- 0.05 vs 1.1 +/- 0.1; #). EGF attenuated both cAI (0.5 +/- 0.04) and vAI (0. 5 +/- 0.03) following SBR. In the waved-2 mice, the highest levels of cAI (3.1 +/- 0.2) and vAI (3.6 +/- 0.3) were noted after SBR. Conclusi ons. Enterocyte apoptosis during adaptation is attenuated by EGF and e xaggerated when the EGF receptor is defective. In addition to enhancin g proliferation, suppression of apoptosis may provide a previously unr ecognized mechanism for the beneficial effect of EGF during intestinal adaptation. (C) 1998 Academic Press.