Induction of urokinase receptor expression in nephrotoxic nephritis

The urokinase receptor (uPAR) is a multifunctional molecule involved in per icellular, fibrinolytic, and proteolytic activities, as well as in cell adh esion and chemotaxis and may play a role in the pathogenesis of tissue remo deling occurring during glomerulonephritis. We analyzed sequentially the ex pression of uPAR by immunohistochemistry and in situ hybridization in an ac celerated model of nephrotoxic nephritis in rats. A strong induction of uPA R mRNA expression was observed in glomeruli as soon as 1 h after nephrotoxi c serum injection. The intensity of glomerular uPAR mRNA and antigen expres sion increased and peaked at 24 h. At that time, numerous glomerular fibrin deposits, monocyte/marcrophage infiltration, and heavy proteinuria were ob served. Fibrin deposition was detected at 6 h, peaked at 24 h, and progress ively declined over the next 3 weeks, while uPAR antigen expression remaine d elevated until the end of the study (3 weeks). By double labeling, we sho wed that the expression of uPAR was mediated by both intrinsic glomerular c ells and infiltrating macrophages. Severe podocytic lesions developed withi n 3 days after antiserum injection, and glomerulosclerosis rapidly progress ed within 2-3 weeks. These results show that glomerular uPAR expression is induced in nephrotoxic nephritis and suggest that uPAR may promote local pr oteolysis and also tissue remodeling, leading to the late development of gl omerulosclerosis. Copyright (C) 2001 S. Karger AG, Basel.