The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa

Abstract

Background & Aims: Apoptosis is especially relevant in the gastrointestinal tract because the mammalian intestinal mucosa undergoes continual epithelial regeneration. Most recently, we confirmed the proapoptotic role of endogenous transforming growth factor (TGF)-β in the developing chick retina as well as in chick ciliary, dorsal root, and spinal motor neurons. In the present study, we determined to establish the role of TGF-β2 and TGF-β3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfβ2+/- and Tgfβ3+/- heterozygous mice. Methods: Intestinal localization of TGF-β2 and TGF-β3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis. Apoptosis was detected by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and proliferation was detected by proliferating cell nuclear antigen stains. Results: TGF-β2 was detected in endocrine cells, whereas TGF-β3 was predominantly found in goblet cells. Programmed cell death was significantly reduced in the intestinal mucosa of Tgfβ2+/- and Tgfβ3+/- heterozygous mice. This decrease in apoptosis was accompanied by an increase in villus length; proliferation, however, seemed to remain unchanged. The level of Bcl-xL and Bcl-2 was significantly up-regulated in Tgfβ2+/- and Tgfβ3+/- mice. Conclusions: Our data show that TGF-β2 and TGF-β3 play an important role in mediating apoptosis in the intestinal mucosa and regulating apoptosis-associated proteins Bcl-xL and Bcl-2 in vivo.