THE EFFECT OF GLUCOSE ON PROTEOGLYCANS PRODUCED BY CULTURED MESANGIALCELLS

Altered proteoglycan metabolism may play a role in the development of diabetic glomerulopathy. This study was conducted to examine the effec ts of glucose on the production and physical characteristics of proteo glycans generated by rat mesangial cells in culture. Rat mesangial cel ls were exposed to elevated glucose media (500 mg/dl) or standard gluc ose media (200 mg/dl) for 8-10 days, and proteoglycan synthesis was de termined using S-35-labeling in conjunction with anion exchange and si zing chromatography. Rat mesangial cells generated predominantly chond roitin/dematan sulfate proteoglycans, with small amounts of heparan su lfate proteoglycans. High glucose did not alter the number of rat mesa ngial cells after 24 h or after 8-10 days, compared with cells grown u nder standard glucose conditions. The total amount of glycosaminoglyca n generated and the sizes of the major proteoglycans were not differen t between cultures grown in standard and elevated glucose medium. Leve ls of mRNA for the proteoglycan, biglycan (as assessed by Northern blo t analysis), also were comparable between the standard and elevated gl ucose conditions. Exposure to media high in glucose did not change the rate of secretion of proteoglycans from the cell layer to the medium, but did result in a greater quantity of radiolabeled proteoglycan dep osited in the extracellular matrix. The cell, extracellular matrix and medium proteoglycans isolated from the elevated glucose cultures, con sistently eluted form the anion exchange column at a lower [NaCl] comp ared with those generated under standard glucose conditions, indicatin g a loss of anionic charges. We conclude that exposure of rat mesangia l cells to media high in glucose results in a greater amount of labele d proteoglycan deposited in the extracellular matrix. These proteoglyc ans are the same size but have a lower charge density than those gener ated under standard glucose conditions.