Mechanisms of tissue remodeling in diabetic enteropathy

D'ARPINO MC; SANCHEZ SS; HONORE SM

Mar del Plata, Buenos Aires

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2015

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

The clinical course of diabetic enteropathy is highly heterogeneous and often unpredictable, with multiple complications as diarrhea, constipation or fecal incontinence. All these problems are manifestations of an intestinal tissue remodeling. Using an STZ-induced rat model, we showed that extracellular matrix macromolecules (ECM) such as collagen and fibronectin are progressively altered during diabetic progression in the whole intestinal wall.Increased expression of mesenchymal markers (vimentin and a-SMA) and significant up-regulation of inducers and mediators TGF-b1, TGFRs, p-Smad2/3 in the mucosa were also observed. In vivo results were correlated with increased collagen III synthesis both at the mRNA and protein levels, without alteration of collagen I production in high glucose-treated fibroblasts in culture. This suggests an active role of these cells in fibrogenic response in vivo.At the muscle layer a change from the contractile to a secretory phenotype of smooth muscle cells (SMC), an imbalance between MMPs/TIMPs activities and a deregulated TGF-b1 signaling were evident in STZ-induced rats.Taken together, these data give a window into the process of diabetic intestinal fibrosis where phenotypic changes in fibroblasts and in SMCs are responsible of the intestinal wall remodeling with a TGF signaling involvement.