Transcriptome and single-cell profiling of the mechanism of diabetic kidney disease

BACKGROUND The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome may play an important role in diabetic kidney disease (DKD). However, the exact link remains unclear. AIM To investigate the role of the NLRP3 inflammasome in DKD. METHODS Using datasets from the Gene Expression Omnibus database, 30 NLRP3 inflammasome-related genes were identified. Differentially expressed genes were selected using differential expression analysis, whereas intersecting genes were selected based on overlapping differentially expressed genes and NLRP3 inflammasome-related genes. Subsequently, three machine learning algorithms were used to screen genes, and biomarkers were identified by overlapping the genes from the three algorithms. Potential biomarkers were validated by western blotting in a db/db mouse model of diabetes. RESULTS Two biomarkers, sirtuin 2 (SIRT2) and caspase 1 (CASP1), involved in the Leishmania infection pathway were identified. Both biomarkers were expressed in endothelial cells. Pseudo-temporal analysis based on endothelial cells showed that DKD mostly occurs during the mid-differentiation stage. Western blotting results showed that CASP1 expression was higher in the DKD group than in the control group (P < 0.05), and SIRT2 content decreased (P < 0.05). CONCLUSION SIRT2 and CASP1 provide a potential theoretical basis for DKD treatment.