Epidermal growth factor alters the bax:bcl-w ratio following massive small bowel resection.
BACKGROUND
Following massive small bowel resection (SBR), the expression of bax and bcl-w is associated with increased enterocyte apoptosis. Epidermal growth factor (EGF) has been shown to enhance enterocyte proliferation and retard apoptosis in the adapting bowel. This study examined the effect of EGF on the expression of these bcl-2 family members during adaptation.


METHODS
Mice (C57Bl/6; n = 38) underwent a 50% SBR or sham operation and then were randomized to receive twice-daily orogastric saline or EGF (50 microg/kg/day). After 3 days, the remnant ileum was removed, apoptotic 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 SBR and altered the ratio of bax to bcl-w in favor of cell survival.


CONCLUSIONS
Following massive small bowel resection, EGF retards rates of enterocyte apoptosis and modifies the expression of bcl-2 family members. By decreasing bax and increasing bcl-w expression, the balance between pro- and 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.
Stern
L E
LE
Division of Pediatric Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Falcone
R A
RA
Huang
F
F
Kemp
C J
CJ
Erwin
C R
CR
Warner
B W
BW
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D020895:Enterocytes / Q000737:chemistry / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012778:Short Bowel Syndrome / Q000503:physiopathology / Q000601:surgery; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D004815:Epidermal Growth Factor