Integration of transcriptomics and metabolomics reveals the molecular mechanisms underlying the effect of nafamostat mesylate on rhabdomyolysis-induced acute kidney injury

To investigate the role and mechanisms of action of nafamostat mesylate (NM) in rhabdomyolysis-induced acute kidney injury (RIAKI). RIAKI was induced in rats using glycerol, which were assigned into three groups: control group (CN), RIAKI group (RM), and NM intervention group (NM). Blood and kidney samples were collected for biochemical and histopathological assay. Inflammatory cytokines were assessed using ELISA. Cell apoptosis was detected with TUNEL assay. Transcriptomic and metabolomic analysis was performed to profile the expression of genes and metabolites after NM intervention. The key differentially expressed Genes (DEGs) were validated using qPCR. The Kyoto Encyclopedia of Genes and Genomes database and conjoint analysis of transcriptome and metabolome were used to analyze the enriched pathways of DEGs and differential metabolites. NM protects the kidneys against RIAKI, which is mainly associated with NM mediated regulation of glutathione metabolism, inflammatory response, ferroptosis-related pathways, and the related key DEGs, including Anpep, Gclc, Ggt1, Mgst2, Cxcl13, Rgn, and Akr1c1. Targeting these genes might emerge as a potential molecular therapy for RIAKI.