TGF-beta/Smad signaling and gangliosides in diabetic intestinal dysfunction

D ARPINO M. C.; HONORÉ S.M.; PEREZ AGUILAR R.C.; GENTA S.B.; SANCHEZ S.S.

Tafí del Valle, Tucumán, Argentina

Congreso; XXVII Annual Scientific Meeting; 2010

Asociación de Biología de Tucumán

Intestinal disorders are common complications in the diabetic state. However, the cellular and molecular mechanisms leading to intestinal dysfunction are not yet fully understood. In this study, we investigated the involvement of cell surface gangliosides and TGFbeta1/Smad signaling pathway in the alterations of the large intestine in a model of experimental diabetes in rodents. Morphological and functional studies indicated that diabetes causes a deregulation of proliferative and apoptotic processes in the mucosa and muscular layers of the bowel. Immunohistochemical and westernblot analysis indicated a significant increase in the expression of TGF-beta1 ligand, type 1 receptor (TGF-RI) and phosphorylated Smad2/3 protein in the muscle layer of the diabetic animals. These results suggest an increased activity of this signaling pathway. The ganglioside analysis by HPTLC showed quantitative changes in the expression pattern of these molecules with a significant increase in GM1, GM2, GD3 (pro- poptotic), GT1b gangliosides and a decrease in GD1a ganglioside. We propose a regulatory role for these molecules in the pathogenesis of diabetic intestinal dysfunction.