Effect of transforming growth factor-alpha on intestinal adaptation in a rat model of short bowel syndrome.
OBJECTIVE
TGF-alpha has recently been shown to stimulate enterocyte proliferation. In the present study we investigated the effect of TGF-alpha on enterocyte proliferation and loss via apoptosis and its effects on intestinal adaptation in a rat following massive bowel resection.


METHODS
Male Sprague-Dawley rats underwent bowel transection and reanastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group) and were treated with intraperitoneal TGF-alpha (75 microg/kg) from the ninth postoperative day (SBS-TGF-alpha group). Parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. Statistical significance was determined by ANOVA with a P < 0.05 considered significant.


RESULTS
SBS-TGF-alpha rats demonstrated a significant increase (vs SBS) in duodenal, jejunal, and ileal overall bowel and mucosal weights; ileal mucosal DNA and protein; and jejunal and ileal villus height. SBS-TGF-alpha rats also showed an increased cell proliferation index in jejunum (704 +/- 43 vs 499 +/- 63 BrdU-positive cells/10 crypts, P < 0.05) and ileum (715 +/- 84 vs 529 +/- 40 BrdU-positive cells/10 crypts, P < 0.05) and decreased apoptotic index in ileum (8.7 +/- 1.1 vs 21.8 +/- 3.2 apoptotic cells/1,000 villus cells, P < 0.05) compared to SBS animals.


CONCLUSIONS
In a rat model of SBS, TGF-alpha enhances intestinal adaptation. Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis.
Sukhotnik
Igor
I
Rappaport Faculty of Medicine, Technion, Carmel Medical Center, Haifa 34362, Israel.
Yakirevich
Evgeny
E
Coran
Arnold G
AG
Siplovich
Leonardo
L
Krausz
Michael
M
Hirsh
Mark
M
Sabo
Edmund
E
Shiloni
Eitan
E
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D011506:Proteins; D016211:Transforming Growth Factor alpha; D004247:DNA