Co-differential genes between DKD and aging: implications for a diagnostic model of DKD.

OBJECTIVE: Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM) that is closely related to aging. In this study, we found co-differential genes between DKD and aging and established a diagnostic model of DKD based on these genes.

METHODS: Differentially expressed genes (DEGs) in DKD were screened using GEO datasets. The intersection of the DEGs of DKD and aging-related genes revealed DKD and aging co-differential genes. Based on this, a genetic diagnostic model for DKD was constructed using LASSO regression. The characteristics of these genes were investigated using consensus clustering, WGCNA, functional enrichment, and immune cell infiltration. Finally, the expression of diagnostic model genes was analyzed using single-cell RNA sequencing (scRNA-seq) in DKD mice (model constructed by streptozotocin (STZ) injection and confirmed by tissue section staining).

RESULTS: First, there were 159 common differential genes between DKD and aging, 15 of which were significant. These co-differential genes were involved in stress, glucolipid metabolism, and immunological functions. Second, a genetic diagnostic model (including IGF1, CETP, PCK1, FOS, and HSPA1A) was developed based on these genes. Validation of these model genes in scRNA-seq data revealed statistically significant variations in FOS, HSPA1A, and PCK1 gene expression between the early DKD and control groups. Validation of these model genes in the kidneys of DKD mice revealed that Igf1, Fos, Pck1, and Hspa1a had lower expression in DKD mice, with Igf1 expression being statistically significant.

CONCLUSION: Our findings suggest that DKD and aging co-differential genes are significant in DKD diagnosis, providing a theoretical basis for novel research directions on DKD.