BMP/SMAD signalling in intestinal tract during diabetes

HONORÉ S.M.; GENTA S.B.; SÁNCHEZ S. S.

Pinamar, Buenos Aires, Argentina

Congreso; X Congress of the Panamerican Association for Biochemistry and Molecular Biology (PABMB), the XLI Annual Meeting of the Argentine Society for Biochemistry and Molecul; 2005

Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor beta and activins. BMPs act early in the gut morphogenesis, also regulate specification and differentiation in the developing enteric nervous system (ENS) and have recently been considered to play a pivotal role in limiting the number of enteric neurons and promote the development of a particular subset. Gastrointestinal disorders are common complications in diabetic state. Under our experimental conditions we observed an increase in apoptosis and a decrease in proliferation within the muscular layer particularly at myenteric ganglia level. This results are in correlation with a significant decrease in the expression of Vasoactive intestinal polypeptide mRNA, an inhibitory transmitter secreted by a subpopulation neurons. These facts may contribute in part to the abnormal gut motility observed in diabetes. In this study, we have investigated the possible involvement of BMPs in the gut of diabetic rodents. We show that BMP4 expression is active in the sumbmucosae and in the ENS of normal gastrointestinal tract but is more widespread in diabetic gut. Furthermore, the mRNA profiles for BMP ligands, receptors and cytoplasmic mediators were significantly altered during diabetic animals. We observed an induction of BMPRII, BMPRI and Smad3 and also a downregulation of BMP 2. Collectively, our data demonstrate for the first time active BMP/Smad signaling in diabetic gut and thus raise the possibility that BMPs could play a determining role in intestinal pathophysiology during diabetes. We are currently investigating what BMP ligand is involved in the activation of this pathway.