DYS - REGULATIONOF EXTRACELLULAR MATRIX PROTEINS TURNOVER BY HIGH GLUCOSE CONCENTRATIONSIN CULTURED HUMAN GLOMERULAR MESANGIAL CELLS

Diabetic glomerulopathy is generally believed to be the major cause for the development of chronic renal failure in diabetes mellitus. Diabetic glomerulosclerosis is characterized by the accumulation of extracellular matrix proteins such as fibronectin and type IV collagen in the mesangium. In this study, the effect of high glucose (33.6 mM) on fibronectin and type IV collagen concentrations in the supernatant of human glomerular mesangial cell culture was studied. The concentrations of fibronection and type IV collagen in tissue culture supernatant, assayed by ELISA techniques increased significantly (P<0.01) by the high glucose level (33.6 mM) after 6 days incubation. Direct cell counting and thymidine incorporation methods showed that high glucose concentrations (33.6 mM, 56 mM and 112 mM) inhibit the mesangial cell (MC) proliferation in concentration-dependent manner. To study the osmotic effect of high glucose concentrations, the mesangial cells were also cultured in the presence of manitol and it was found that manitol did not have effect on cellular proliferation but increased fibronectin and type IV collagen concentrations significantly (P<0.05) in the supernatants. These results indicate that the increase of synthesis and/or decrease degradation of fibronectin and type IV collagen by MCs may, in part, result from changes in osmolarity induced by high glucose concentration. These results suggest that elevation of fibronectin and type IV collagen production and/or decrease their degradation by the mesangial cells may play an important role in the accumulation of these extracellular matrix proteins which is common to diabetic glomerulosclerosis.