TGF-β affects enterocyte turnover in correlation with TGF-β receptor expression after massive small bowel resection.
OBJECTIVE
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, Haifa, Israel. igor-dr@internetzahav.net
Igor
I
Sukhotnik
Shani Ben
SB
Lulu
Yulia
Y
Pollak
Jacob
J
Bejar
Arnold G
AG
Coran
Jorge G
JG
Mogilner
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008297:Male; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000601:surgery; D053781:Transforming Growth Factor beta2 / Q000378:metabolism / Q000494:pharmacology*
D018125:Receptors, Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2