Identifying Key Genes and Mechanisms in Active Vitamin D Treatment for Diabetic Kidney Disease

Background: Diabetic kidney disease (DKD) presents a healthcare challenge with limited treatments. Active vitamin D may address DKD-related fibrosis, but its mechanisms are unclear Methods: Utilized scRNA-Seq data from DKD mice treated with calcitriol and bulk RNA data from GEO. Employed Mendelian randomization and enrichment analyses to explore gene-immune cell interactions. Validated key gene expression with scRNA-Seq and GSE30529. Assessed renal function association with NephroseqV5 and confirmed protein expression with the Human Protein Atlas Results: Active vitamin D reduced proliferative cells. Enrichment analyses highlighted FoxO signaling's role. SUMO3 and CD74 emerged as potential markers correlated with immune infiltration. Significant correlations found between SUMO3, CD74, creatinine levels, and eGFR. Confirmed higher SUMO3 and CD74 protein expression in DKD Conclusion: Increased SUMO3 and CD74 expression in DKD is associated with active vitamin D treatment, affecting fibrosis via the FoxO pathway. They could serve as DKD protection markersFigure 1. Cell Annotation and AnalysisFigure 2. Gene Expression and Verification