Protease-activated receptor-2 augments experimental crescentic glomerulonephritis

Leon Moussa, Jim Apostolopoulos, Piers Rupert Davenport, Jorge Tchongue, Peter George Tipping

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Protease-activated receptor-2 (PAR-2) is a cellular receptor expressed prominently on epithelial, mesangial, and endothelial cells in the kidney and on macrophages. PAR-2 is activated by serine proteases such as trypsin, tryptase, and coagulation factors VIIa and Xa. It induces pleiotropic effects including vasodilatation, increasing plasminogen activator inhibitor (PAI-1) expression, mesangial cell proliferation, and cytokine production by macrophages. The role of PAR-2 in renal inflammation was studied in antiglomerular basement membrane antibody-induced crescentic glomerulonephritis (CGN) using PAR-2-deficient (PAR-2/) mice and wild-type littermate controls. PAR-2/ mice had reduced crescent formation, proteinuria, and serum creatinine compared with wild-type mice 21 days after initiation of CGN. Glomerular accumulation of CD4+ T cells and macrophages and the number of proliferating cells in glomeruli were similar in both groups. Glomerular fibrin deposition was significantly reduced in PAR-2/ mice, and this was associated with reduced renal plasminogen activator inhibitor expression and increased renal matrix-metalloprotinase-9 activity. These results demonstrate a proinflammatory role for PAR-2 in CGN that is independent of effects on glomerular leukocyte recruitment and mesangial cell proliferation. PAR-2-mediated augmentation of renal plasminogen activator inhibitor expression and inhibition of matrix-metalloprotinase-9 activity may contribute to increased glomerular fibrin accumulation and glomerular injury in CGN.
Original languageEnglish
Pages (from-to)800 - 808
Number of pages9
JournalAmerican Journal of Pathology
Issue number3
Publication statusPublished - 2007

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Moussa, L., Apostolopoulos, J., Davenport, P. R., Tchongue, J., & Tipping, P. G. (2007). Protease-activated receptor-2 augments experimental crescentic glomerulonephritis. American Journal of Pathology, 171(3), 800 - 808.