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

Objectives: In the present study, we evaluated the effect of transforming growth factor-beta 2 (TGF-beta 2)-enriched diet on enterocyte turnover and correlated it with TGF-beta 2 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-beta 2. 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-beta rats were treated with diet enriched with TGF-beta 2, SBS rats underwent a 75% bowel resection, and SBS TGF-beta rats were fed a diet enriched with TGF-beta 2 after bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. TGF-beta 2r expression in villus tips, lateral villi and crypts was assessed by immunohistochemistry. The effect of TGF-beta 2 on enterocyte turnover for each compartment was evaluated in correlation with TGF-beta 2r expression. Results: Incubation of CaCo-2 cells with TGF-beta 2 resulted in a significant decrease in cell viability and increased cell apoptosis. TGF-beta 2r expression in crypts increased in SBS rats (vs sham) and was accompanied by decreased cell proliferation and increased cell apoptosis following TGF-beta 2 administration. A significant decrease in TGF-beta 2r expression at villous tips in SBS rats was accompanied by a decreased cell apoptosis in this compartment following exposure to TGF-beta 2-enriched diet. Conclusions: In a rat model of SBS, the inhibiting effect of TGF-beta 2 on enterocyte turnover correlates with TGF-beta 2 receptor expression along the villus-crypt axis.