Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity

Area of Science:

• Nephrology
• Coagulation Cascade
• Inflammation Biology

Background:

• Acute kidney injury (AKI) is linked to hypercoagulability.
• Protease-activated receptor 2 (PAR2) activation by coagulation factors contributes to kidney injury in other contexts.
• The specific role of PAR2 in AKI is not well understood.

Purpose of the Study:

• To investigate the role of PAR2 in cisplatin-induced AKI.
• To determine if PAR2 deficiency protects against cisplatin nephrotoxicity.

Main Methods:

• Cisplatin was administered to wild-type and PAR2-deficient mice.
• Kidney injury markers (BUN, creatinine, tubular injury score) were assessed.
• Inflammatory markers (neutrophil infiltration, cytokine/chemokine gene expression) were measured.
• Apoptotic markers (cleaved caspase-3, Bax/Bcl2 ratio) were evaluated.

Main Results:

• Cisplatin increased kidney tissue factor and PAR2 expression.
• PAR2-deficient mice showed improved kidney function and reduced tubular injury.
• Neutrophil infiltration and pro-inflammatory gene expression were lower in PAR2-deficient mice.
• Apoptosis markers were significantly attenuated in the absence of PAR2.

Conclusions:

• Elevated PAR2 activity worsens cisplatin-induced nephrotoxicity.
• Targeting PAR2 represents a promising therapeutic strategy for treating cisplatin-induced AKI.