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Responsiveness of intestinal epithelial cell turnover to TGF-α 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-α) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-α on enterocyte turnover and correlated it with epidermal-growth factor (...

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Published in:Pediatric surgery international 2008, Vol.24 (1), p.21-28
Main Authors: Sukhotnik, Igor, Mogilner, Jorge G., Shaoul, Ron, Karry, Rahel, Lieber, Michael, Suss-Toby, Edith, Ure, Benno M., Coran, Arnold G.
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description Recent evidence suggests that transforming growth factor alpha (TGF-α) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-α 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-α rats underwent bowel resection and were treated with TGF-α (75 μg/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  
doi_str_mv 10.1007/s00383-007-2038-z
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In the present study, we evaluated the effects of TGF-α 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-α rats underwent bowel resection and were treated with TGF-α (75 μg/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  &lt; 0.05 considered statistically significant. Treatment with TGF-α 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  &lt; 0.05) and decreased apoptosis following TGF-α 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-α (group C). In a rat model of SBS, TGF-α increased enterocyte proliferation and stimulated intestinal adaptation. 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The effect of TGF-α on enterocyte turnover is correlated with EGF receptor expression along the villus–crypt axis.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>17985142</pmid><doi>10.1007/s00383-007-2038-z</doi><tpages>8</tpages></addata></record>
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subjects Animals
Apoptosis
Caspase 3 - metabolism
Cell Proliferation - drug effects
Disease Models, Animal
Enterocytes - drug effects
Enterocytes - metabolism
Enterocytes - pathology
Follow-Up Studies
Gene Expression
Immunohistochemistry
Male
Medicine
Medicine & Public Health
Microscopy, Confocal
Original Article
Pediatric Surgery
Pediatrics
Rats
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor - biosynthesis
Receptor, Epidermal Growth Factor - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Short Bowel Syndrome - drug therapy
Short Bowel Syndrome - metabolism
Short Bowel Syndrome - pathology
Surgery
Transforming Growth Factor alpha - therapeutic use
title Responsiveness of intestinal epithelial cell turnover to TGF-α after bowel resection in a rat is correlated with EGF receptor expression along the villus–crypt axis
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