Down-regulation of wnt/beta-catenin signaling in diabetic intestine

HONORÉ S.M.; ZELARAYÁN L.C.; GENTA S.B.; SÁNCHEZ S. S.

Puerto Madryn, Argentina

Congreso; XLVI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology (SAIB); 2010

SAIB

Wnt pathway controls diverse biological processes during embryonic development and is required for adult tissue maintenance. In the intestine, the canonical Wnt signaling cascade plays a crucial role in driving the proliferation of epithelial cells. Despite, little is known about this pathway in the muscle layer of normal and diabetic adult intestine. We examined the Wnt signaling profile in the intestine of an experimental model of diabetes in rodents. The expression of Wnt1 and 3a, as well as the intracellular signal transducers beta-catenin and Tcf-4 was analyzed by quantitative real-time (q)RT-PCR, western blot and Immunohistochemical studies. Our analysis showed high expression of these signaling components in normal adult intestine. In normal muscle layer, beta-catenin was localized in the smooth muscle and neuronal cells. Diabetes produced a dramatic fall of the intracellular transducers beta-catenin and Tcf-4 with apoptotic process in the myenteric neurons. In addition, the analysis of the Wnt target gene Cx43, also demonstrated a reduced expression of this protein suggesting an altered gap junction coupling. All findings togheter showed a down-regulation of Wnt/ beta-catenin signaling in diabetic intestinal muscle layer.