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.


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.
Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, 45229-3039, USA.
M A
MA
Helmrath
C E
CE
Shin
C R
CR
Erwin
B W
BW
Warner
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D007422:Intestines / Q000166:cytology / Q000502:physiology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011184:Postoperative Period
D004815:Epidermal Growth Factor; D066246:ErbB Receptors