Differential expression of matrix metalloproteinases and their tissue inhibitors in diabetic colon

D ARPINO M.C.; SÁNCHEZ S.S.; GENTA S.B.; SÁNCHEZ S.S.

Rosario, Santa Fe

Congreso; L Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2014

Argentine Society for Biochemistry and Molecular Biology

Diabetes is characterized by alterations of intestinal wall with the thickening of the smooth muscle layer and excessive extracellular matrix (ECM) deposition. The cytokine TGF-b1 appears critical in this process regulating ECM production and turnover. We have recently shown that smooth muscle cells from diabetic intestine express significantly higher amounts of TGF-b1, TGFb RII and the intracellular effector p-Smad2/3. Matrix metalloproteinases (MMPs) are important enzymes of ECM remodeling and growth factors activity. Now, we report that muscle layer of diabetic intestine have significantly lower constitutive expression of MMP-2 and MMP-9 transcripts together with localized collagen III and fibronectin deposition. Also diabetic smooth muscle layer expressed lower amounts of tissue inhibitor of metalloproteinase (TIMP)-1 compared to normal tissue. Interestingly, the expression of specific contractile markers of smooth muscle cells (a-SMA, Smoothelin and MYH-11) was down regulated in diabetic colon indicating a phenotypic change. These studies illustrate a potential mechanism by which differential expression of TGF-b may lead to excessive deposition of ECM in the intestinal smooth muscle layer via the imbalance between MMPs and TIMPs activities and changes in cell phenotype that result from hyperglycemic environment.