Paracrine factors involved in diabetic intestinal dysfunction

D ARPINO M. C.; HONORÉ S. M.; LUQUE, M. E.; SÁNCHEZ S. S.

Mendoza, Argentina

Congreso; XLVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology (SAIB).; 2012

Sociedad Argentina de Bioquímica y Biología molecular (SAIB).

Diabetic intestinal dysfunction is a well-established complication of diabetes mellitus. Bone morphogenetic protein-7 (BMP-7) and TGF-beta1 are growth and differentiation factors which belong to the TGF-beta 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 disfunction, could be consequence in part of a defect in the TGF family members homeostasis. The principal change in diabetes was an up-regulated TGF-beta/Smad signaling in the large intestine. TGF-beta1 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-beta1/BMP-7 signalling at the intestinal muscle layer leading to a fibrotic process at early stage of the disease.