The EGF\EGF-receptor axis modulates enterocyte apoptosis during intestinal adaptation.

BACKGROUND: Adaptation after small bowel resection (SBR) is characterized by a new set point in the balance of enterocyte proliferation and apoptosis. Since epidermal growth factor (EGF) augments both proliferation 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 reanastomosis) and then were given EGF (50 microg/kg/day) or saline by orogastric gavage. At 1 week, a proliferation index (PI) was measured in the ileum by BrdU uptake and an apoptosis index in crypts (cAI) and villi (vAI) scored by counting apoptotic bodies in enterocytes. In other experiments, AI was scored after SBR in mice with defective receptors (waved-2). Results are expressed as means +/- SE and evaluated statistically using ANOVA. # denotes P < 0.001.
RESULTS: Following SBR, EGF increased PI (40 +/- 2% vs 50 +/- 1% BrdU + cells; #), villus height (252 +/- 4 micro(m) vs 401 +/- 15 micro(m); #), and crypt depth (77.3 +/- 1.5 micro(m) vs 120.8 +/- 5 micro(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.
CONCLUSIONS: Enterocyte apoptosis during adaptation is attenuated by EGF and exaggerated when the EGF receptor is defective. In addition to enhancing proliferation, suppression of apoptosis may provide a previously unrecognized mechanism for the beneficial effect of EGF during intestinal adaptation. Copyright 1998 Academic Press.