PARACRINE FACTORS INVOLVED IN DIABETIC INTESTINAL DYSFUNCTION

D'ARPINO MC, HONORÉ SM, LUQUE ME, GENTA SB, SÁNCHEZ SS

MENDOZA

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIONES EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR; 2012

Diabetic intestinal dysfunction is a well-established complication of diabetes mellitus. Bone morphogenetic protein-7 (BMP-7) and TGF-β1 are growth and differentiation factors which belong to the TGF-β superfamily of proteins. Despite, little is known about this pathway in the muscle layer of normal and diabetic adult intestine. Using an experimental model of diabetes in rodents, we explored the hypothesis that diabetic intestinal dysfunction, could be consequence in part of a defect in the TGF family members homeostasis. The principal change in diabetes was an up-regulated TGF-β/Smad signalling in the large intestine. TGF-β1 and TGF-RII receptor were increased in the diabetic muscle layer at mRNA and protein level. P-Smad2/3 protein was distributed throughout the muscle, but the highest levels of active protein were associated with myenteric cells. Our analysis showed down-regulated BMP-7 protein expression in diabetic muscle layer. We also observed that diabetes environment upregulates extracellular matrix deposition in the intestinal muscle layer. An increased synthesis of fibronectin and type III collagen in smooth muscle cells was also observed. Diabetes causes an imbalance in TGF-β1/BMP-7 signalling at the intestinal muscle layer leading to a fibrotic process at early stage of the disease.