Responsiveness of intestinal epithelial cell turnover to TGF-alpha after bowel resection in a rat is correlated with EGF receptor expression along the villus-crypt axis.
Recent evidence suggests that transforming growth factor alpha (TGF-alpha) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-alpha on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-alpha rats underwent bowel resection and were treated with TGF-alpha (75 microg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-alpha resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 +/- 0.013 vs 0.010 +/- 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 +/- 8 vs 138 +/- 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-alpha administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 +/- 0.002 vs 0.029 +/- 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 +/- 0.001 vs 0.028 +/- 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-alpha (group C). In a rat model of SBS, TGF-alpha increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-alpha on enterocyte turnover is correlated with EGF receptor expression along the villus-crypt axis.
Sukhotnik
Igor
I
Technion-Israel Institute of Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Bnai Zion Medical Center, Haifa, Israel.
Mogilner
Jorge G
JG
Shaoul
Ron
R
Karry
Rahel
R
Lieber
Michael
M
Suss-Toby
Edith
E
Ure
Benno M
BM
Coran
Arnold G
AG
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005500:Follow-Up Studies; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000627:therapeutic use*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D053148:Caspase 3