Tissue‐type plasminogen activator and its inhibitor in human glomerulonephritis

Abstract

We carried out an immunohistochemical study of tissue-type plasminogen activator (PA) and urokinase-type PA, and their inhibitors, PA inhibitor-1 and PA inhibitor-2, using renal biopsy specimens obtained from 86 patients with various forms of glomerulonephritis. The controls were four normal renal tissue specimens. On immunofluorescent observation, granular staining for tissue-type PA was found to be distributed along the glomerular capillary walls. The fluorescence was weak in the normal renal tissue and occasionally intense in the tissues of patients with IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA inhibitor-1 was abundant in the glomerular epithelial cells and scarce in the mesangial area and glomerular capillary lumens of the normal renal tissues. This was confirmed by immunoelectron microscopy using gold staining. The fluorescence of PA inhibitor-1 was weaker in some specimens of nephritic tissues than in the normal renal tissues. Urokinase-type PA and PA inhibitor-2 were negative within the glomeruli in all the specimens. In the glomerulonephritic tissues which were fibrin deposition-positive, tissue-type PA expression in the glomeruli tended to be strong. An association between fibrin deposition and PA inhibitor-1 staining was not clear. These data suggest that expression of tissue-type PA in the glomeruli increases in association with fibrin deposition.

Effect of dsRNA on Mesangial Cell Synthesis of Plasminogen Activator Inhibitor Type 1 and Tissue Plasminogen Activator

“…This might result in an imbalance in plasmin activation and a reduced dissolution of fibrin and turnover of ECM proteins with generation of glomerular fibrosis. The observation that activation of TLR3 increases expression of both PAI-1 and t-PA is consistent with in vitro findings in several forms of glomerulonephritis [32]; it can be explained by the fact that physiologically both profibrotic and profibrinolytic components are necessary for regeneration and healing in glomerular inflammatory processes. The development of matrix abnormalities might not be specific for virally induced glomerular injury but is supposed to be characteristic for any form of immune-mediated glomerular disease.…”

mRNA expression of urokinase and plasminogen activator inhibitor‐1 in human crescentic glomerulonephritis

“…Positive immunostaining for tPA has been described in normal human glomeruli 4 , 6 , 8 , 9 . uPA 8 , 9 and PAI‐1 6 , 8 antigens are not generally detected in the normal kidney. Cultured GECs, however, express uPA protein 4 , 10 and uPA mRNA 11 …”

Enhanced Expression of Plasminogen Activator Inhibitor 1 in Patients with Nephrotic Syndrome

“…The presence of PAI-1 in normal glomeruli is controversial. Several investigators have reported the absence of PAI-1 in normal glomeruli [24, 25, 26], whereas Aya et al [27]have demonstrated immunostaining of PAI-1 in glomerular epithelial cells, in the mesangial area, and along the capillary walls. Immunoreactivity of PAI-1 does appear in diseased kidneys, including crescentic glomerulonephritis, IgA nephropathy, thrombotic microangiopathy, and membranous nephropathy, occasionally coexisting with fibrin deposits or vitronectin [24, 25, 26, 27, 28].…”