Protease-activated receptor-2 augments experimental crescentic glomerulonephritis.

Area of Science:

• Nephrology
• Immunology
• Molecular Biology

Background:

• Protease-activated receptor-2 (PAR-2) is expressed in kidney cells and macrophages.
• PAR-2 activation leads to varied effects, including inflammation and altered protein expression.
• Its specific role in kidney inflammation, particularly crescentic glomerulonephritis (CGN), requires further elucidation.

Purpose of the Study:

• To investigate the role of PAR-2 in experimental anti-glomerular basement membrane antibody-induced crescentic glomerulonephritis (CGN).
• To determine if PAR-2 deficiency impacts disease severity and specific pathological features in CGN.

Main Methods:

• Utilized PAR-2-deficient (PAR-2(-/-)) mice and wild-type littermate controls.
• Induced CGN using anti-glomerular basement membrane antibodies.
• Assessed kidney injury markers (proteinuria, serum creatinine), crescent formation, cellular infiltration, proliferation, fibrin deposition, PAI-1, and MMP-9 activity.

Main Results:

• PAR-2(-/-) mice exhibited significantly reduced crescent formation, proteinuria, and serum creatinine levels compared to wild-type controls.
• Glomerular accumulation of T cells and macrophages, and cell proliferation rates were comparable between groups.
• PAR-2 deficiency led to reduced glomerular fibrin deposition, decreased renal plasminogen activator inhibitor (PAI-1) expression, and increased renal matrix-metalloproteinase-9 (MMP-9) activity.

Conclusions:

• PAR-2 plays a significant proinflammatory role in CGN, independent of leukocyte recruitment and mesangial cell proliferation.
• PAR-2 contributes to kidney injury by increasing PAI-1 expression and inhibiting MMP-9 activity, thereby promoting fibrin accumulation.
• Targeting PAR-2 may offer a therapeutic strategy for managing renal inflammation and injury in CGN.