Expression of glomerular plasminogen activator inhibitor type 1 in glomerulonephritis

Plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) are the major regulators of plasmin generation. Glomerular PAI-1/tPA balance is involved in extracellular matrix turnover, as well as fibrin deposition in glomeruli. Renal biopsy specimens were obtained from 80 patients with either primary or secondary glomerulonephritis (10 patients, minimal change nephrotic syndrome; 6 patients, focal segmental glomerulosclerosis [FSGS]; 10 patients, membranous nephropathy [MN]; 24 patients, mesangial proliferative glomerulonephritis; 15 patients, lupus nephritis; 14 patients, diabetic nephropathy; and 1 patient, membranoproliferative glomerulonephritis). We quantified glomerular PAI-1 and tPA messenger RNA (mRNA) by competitive polymerase chain reaction. We also determined PAI-1 mRNA localization by in situ hybridization. Glomerular PAI-1 mRNA levels in patients with FSGS and MN were significantly greater than those of controls. There was a sixfold increase in PAI-1-tPA mRNA ratio in patients with MN compared with the control group. In addition, glomerular PAI-1 mRNA level correlated with level of proteinuria. Conversely, there was no difference in tPA mRNA levels among types of glomerulonephritis. These results suggest that suppressed glomerular fibrinolytic and proteolytic activity may be associated with the pathogenesis of glomerulonephritis, especially in FSGS and MN.