An integrative proteomics metabolomics based strategy reveals the mechanisms involved in wasp sting induced acute kidney injury

The pathophysiological mechanisms involved in wasp-sting-induced acute kidney injury (AKI) remain largely unknown. Here, we combined proteomics and metabolomics to investigate the mechanisms behind multiple wasp sting-induced AKI. Interestingly, we found many differentially abundant proteins in the serum of AKI group compared with that of the non-AKI and control groups, involved in several metabolic pathways and the regulation of cellular processes. In addition, we also detected differentially abundant metabolites in the AKI group; among them many were involved in the glycerophospholipid metabolic pathway (the key pathway in the context of AKI): 50 metabolites, all downregulated in the AKI group. Importantly, the convergent analysis of metabolomics and proteomics data revealed that biomarkers of rhabdomyolysis (CA 3, MYL3, and LDH) and hemolysis (ALT and LDH) were integrated into a regulatory network with phospholipid metabolism products in the AKI group, indicating that wasp sting-induced AKI is secondary to rhabdomyolysis and intravascular hemolysis. Of note, such a phenotype suggests the disruption of the membrane of skeletal muscle cells and red blood cells mediated by the phospholipase A1 (PLA1), PLA2, and mastoparan in the wasp venom, via the disruption of membrane glycerophospholipids. Overall, our results highlight a potential new mechanism behind wasp sting-induced AKI and suggest that PLA inhibitors may be potential agents for the treatment of this condition.