BMPs regulate the survival of enteric cells in adult gut

HONORÉ S.M.; GENTA S.B; VILLECCO E.I.; SÁNCHEZ S.S.

Cancún, Mexico

Congreso; First Pan American Congress in Developmental Biology; 2007

Society for Developmental Biology, Latin American Society for Developmental Biology and Sociedad Mexicana de Biologia del Desarrollo

Bone morphogenetic proteins (BMPs) are critical molecules during gut morphogenesis. However, little is known about their participation in the homeostasis of adult gut and their possible role in disease. In a previous work we have described that pathological lesion occurs in the diabetic gut; specially a reduction of myenteric neurons by apoptotic process has been noted in short term-diabetes. Here, we investigated the BMP/Smad signaling at myenteric system (MS) level in an experimental model of diabetes in mouse. We examined at the mRNA and protein levels, the expression of BMPs, BMP receptors and intracellular effectors Smad in small intestine of normal and diabetic gut. The results demonstrate de presence of BMP molecules in normal adult intestine. The diabetic state produced changes in the expression of all molecules analized. Interestingly, BMP4 expression profile was strongly altered and was restricted to both mucosae and submucosae cells in jejunum of normal animals. Meanwhile, BMP4 staining was mainly present surrounding MS in smooth muscle layer of diabetic animals. The neuroenteric cells of diabetic mouse also expressed levels of phosphorilated Smad1 (Smad1-P) indicative of active BMP/Smad signaling. This was in contrast to healthy ganglia cells, which were devoid of immunoreactivity. In addition, analysis by Laser scanning microscopy evidenced that BMP4 and Smad1-P proteins colocalized with TUNEL positive cells in diabetic MS. Taken together these data suggest that BMPs/Smad signaling plays an important role in the apoptotic process in the diabetic gut.