TGF- Affects Enterocyte Turnover in Correlation With TGF- Receptor Expression After Massive Small Bowel Resection

Sukhotnik, Igor*; Lulu, Shani Ben*; Pollak, Yulia*; Bejar, Jacob; Coran, Arnold G.; Mogilner, Jorge G.*,†

Journal of Pediatric Gastroenterology & Nutrition: December 2012 - Volume 55 - Issue 6 - p 721–727
doi: 10.1097/MPG.0b013e318263ec18
Original Articles: Gastroenterology

Objectives: In the present study, we evaluated the effect of transforming growth factor-beta 2 (TGF-β2)-enriched diet on enterocyte turnover and correlated it with TGF-β2 receptor expression along the villus–crypt axis in a rat model of short bowel syndrome (SBS).

Methods: CaCo-2 cells were incubated with increasing concentrations of TGF-β2. Alamar Blue reduction test was used for investigation of cell viability and evaluation of cell apoptosis was assessed by flow cytometry. Male rats were divided into 4 groups: Sham rats underwent bowel transection, Sham TGF-β rats were treated with diet enriched with TGF-β2, SBS rats underwent a 75% bowel resection, and SBS TGF-β rats were fed a diet enriched with TGF-β2 after bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. TGF-β2r expression in villus tips, lateral villi and crypts was assessed by immunohistochemistry. The effect of TGF-β2 on enterocyte turnover for each compartment was evaluated in correlation with TGF-β2r expression.

Results: Incubation of CaCo-2 cells with TGF-β2 resulted in a significant decrease in cell viability and increased cell apoptosis. TGF-β2r expression in crypts increased in SBS rats (vs sham) and was accompanied by decreased cell proliferation and increased cell apoptosis following TGF-β2 administration. A significant decrease in TGF-β2r expression at villous tips in SBS rats was accompanied by a decreased cell apoptosis in this compartment following exposure to TGF-β2-enriched diet.

Conclusions: In a rat model of SBS, the inhibiting effect of TGF-β2 on enterocyte turnover correlates with TGF-β2 receptor expression along the villus–crypt axis.

*Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology

Departments of Pathology

Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel.

Address correspondence and reprint requests to Igor Sukhotnik, MD, Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St, P.O.B. 4940, Haifa 31048, Israel (e-mail: igor-dr@internet-zahav.net).

The work was supported by the Israel Science Foundation (ISF no. 1135/08 from 1 October 2010) and Albert Goodstein research grants.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN