Cysteinyl‐tRNA synthetase is involved in damage of renal tubular cells in ischemia–reperfusion‐induced acute kidney injury via pyroptosis

Abstract Acute kidney injury (AKI) is a significant global healthcare burden but lacks specific and effective treatment. Renal tubular cells damage is central to ischemia‐reperfusion injury (IRI) induced AKI. It is critical to clarify the initiation mechanisms of renal IRI and develop early intervention targets of AKI. This study used label‐free quantification proteomic analysis to identify new targets in AKI‐related renal tubular injury and investigate the potential mechanisms. We discovered significant changes in cysteinyl‐tRNA synthetase (CARS) in renal tubular cell during IRI. Considering the involvement of CARS in ATP metabolism and the close correlation between ATP and pyroptosis, we further explored pyroptosis phenotype with and without CARS intervention as well as the expression of CARS during pyroptosis activation and inhibition. Our findings suggest that CARS expression decreased over time and is linked to pyroptosis. Modifying CARS affects ATP metabolism and alters the expression of pyroptosis‐related proteins during H/R and IRI treatments. Regulating pyroptosis may influence CARS expression during IRI treatment. Overall, CARS is associated with renal tubular damage from ischemia‐reperfusion injury, possibly involving pyroptosis, though the regulatory mechanism remains unclear.