TGF-b signaling in diabetic intestinal mucosa.

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

San Miguel de Tucumán, Tucumàn, Argentina.

Congreso; XLV Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology (SAIB); 2009

SAIB

Long-term diabetes is associated with morphological, functional, and metabolic alterations in the small intestine. Using an experimental model of diabetes in rodents, we explored the hypothesis that diabetic intestinal disfunction, could be consequence in part of a defect in the mucosa TGF-beta system. The principal change in diabetes was an up-regulated TGF-beta/Smad signalling in the small intestine. TGF-beta1 and TGF-âbetareceptors RII were increased in the diabetic mucosa at mRNA and protein level. p-Smad2/3 protein was distributed throughout the mucosa, but the highest levels of active protein were associated with mesenchymal cells. This cellular population, predominantly SMA+/vimentina+ myofibroblasts , were incresed in the mucosa of diabetic animals. We also observed that diabetes environment upregulates extracellular matrix (ECM) deposition in the intestinal mucosa. Proteins such as type IV collagen and laminin were accumulated throughout the basal lamina, whereas fibronectin was restricted to lamina propia. An increased syntesis of type III collagen in mesenchymal cells was also observed. Collectively all the data showed that the TGF-beta1 deregulation in diabetic mucosa is associated with the emergence of cell with myofibroblast phenotype and  ECM accumulation. Diabetes causes an imbalance in the normal mucosa remodelling, leading to a fibrotic process at early stage of the disease.