Phenotype changes in the intestinal muscle layer during diabetes

D'ARPINO M.C.; LUQUE M. E.; SANCHEZ S.S.; HONORÉ S.M.

San Miguel de Tucumán

Congreso; XXX Jornadas Asociación de Biología de Tucumán; 2013

Asociación de Biología de Tucumán

Intestinal smooth muscle cells (ISMCs) are fully differentiated cells that harbour a unique repertoire of contractile proteins such as smooth muscle alpha actin (alpha-SMA), smooth muscle myosin heavy chain (SM-MHC) isoforms and smoothelin required for the motility function. ISMCs behaviour depends on several genetic and environmental cues. Transforming growth factor beta (TGF-b) proteins are multifunctional cytokines regulating diverse cellular functions: growth, apoptosis, extracellular matrix (ECM) synthesis and differentiation. Using an experimental model of diabetes and TUNEL, RT-PCR, western blot and Immunohistochemical techniques, we examined changes in morphology, proliferation, apoptosis and specific contractile marker proteins at the intestinal muscle layer. Our results indicated a significant decrease in the apoptotic process in diabetic animals. No changes in proliferation were observed. A significant decrease in alpha-SMA, MYH11 and smoothelin expression and increased collagen III and fibronectin deposition were evidenced in diabetic muscle layer. In addition, we determined a down regulation in TGF-b1 ligand and TGFRII receptor. The data suggest that diabetic state leads to a change from the contractile phenotype of ISMCs to a secretory phenotype. This might be induced by deregulated TGF-b1 signalling. All these changes could be responsible of motility disorders in the diabetic intestine.