A HIGH-CONCENTRATION OF GLUCOSE ALTERS THE PRODUCTION OF TPA, UPA ANDPAI-1 ANTIGENS FROM HUMAN MESANGIAL CELLS

To elucidate a role of tPA, uPA and PAI-1 for the development of diabe tic glomerulosclerosis, the effect of high glucose concentration on th e production of both basal and thrombin-mediated tPA, uPA and PAI-1 an tigens from human mesangial cells was investigated. The culture of mes angial cells in the presence of high glucose (33 mM) for 11 days resul ted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells gr own in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PA I-1 from the cells grown in either 5 or 33 mM glucose. However, the ma gnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results sugge st that the plasmin activity in mesangial cells may increase under a h igh glucose condition, leading to increased proteolysis of mesangial m atrix. In addition, either fibrinolysis or proteolysis mediated by thr ombin may be altered by high glucose concentration. Therefore, it is p ostulated that the turnover of mesangial matrix may be increased in di abetic nephropathy.