Endogenous BMP signalling in normal ad diabetic mice

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

Los Cocos, Cordoba, Argentina

Workshop; 1st International Workshop: New Concepts in Developmental Biology; 2006

The enteric nervous system (ENS) is derived from neural crest cells that migrate along the gastrointestinal tract to form a network of neurons and glia that are essential for regulating intestinal motility. Despite the number of genes known to play essential roles in ENS development, the participation in adult tissues and under pathologica1 states remains largely unknown. Gastrointestinal disorders are common complications in diabetic state resulting in a loss of enteric neurons and subsequent motility alteration. The molecular etiology of this process is not known yet. BMPs act early in gut morphogenesis particularly regulating specification and differentiation of ENS. In this study, we have investigated the presence of BMP signaling pathway in normal adult gut and their possible involvement in gastrointestinal dysfunction in experimental model of diabetes. Under our experimental conditions we observed alterations in the expression of Vasoactive intestinal polypeptide and Substance P mRNAs two neuronal transmitters implicated in smooth muscle contraction.                We showed that BMP4 expression is active in the submucosa and in the ENS of normal intestine but is more widespread in diabetic gut Furthermore, the mRNA profiles for BMP ligands, receptors and cytoplasmic mediators were significantly altered during diabetes. We observed change in levels of BMP 2 and BMP4 mRNA, in contrast any variation was shown for BMP6 mRNA. An increase of BMP type I, II receptors and Smadl expression was also reported. Collectively, our data demonstrate for the first time active BMP/Smad signaling in adult gut. Moreover, diabetic gut shows a deregulation of this signaling pathway. Thus raises the possibility that BMPs could play a determining role in the pathophysiology of diabetic gut.