EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON PLASMINOGEN ACTIVATORSAND PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN RENAL GLOMERULAR CELLS

Recent evidence suggests that the balance between serine proteases and their inhibitors is central to the maintenance of the glomerular extr acellular matrix. We have characterised the urokinase type and the tis sue type plasminogen activators (PA) and their inhibitor, PAI-1, secre ted from glomerular epithelial and mesangial cells as well as their co -cultures and have investigated the effect of transforming growth fact or-beta1 (TGF-beta1) on the production of such species. Similar data w ere derived from whole glomeruli suspensions. TGF-beta1 increased PAI- 1 production significantly in epithelial and mesangial cells as well a s in whole glomeruli, while PA production was decreased; platelet-deri ved growth factor had no effect. These effects are consistent with a p ossible decrease in matrix proteolysis, suggesting a mechanism by whic h TGF-beta1 may enhance mesangial matrix accumulation, a characteristi c of many forms of glomerular disease.