Identification of crucial genes and possible molecular pathways associated with active vitamin D intervention in diabetic kidney disease.

BACKGROUND

A significant cause of advanced renal failure is diabetic nephropathy (DKD), with few treatment options available. Calcitriol shows potential in addressing fibrosis related to DKD, though its molecular mechanisms remain poorly understood. This research seeks to pinpoint the crucial genes and pathways influenced by calcitriol within the scope of DKD-related fibrosis.

METHODS

Single-cell gene expression profiling of calcitriol treated DKD rat kidney tissue and screening of fibrosis-associated cell subsets. Mendelian randomization and enrichment analyses (CIBERSORT, GSVA, GSEA, Motif Enrichment) were used to explore gene-immune cell interactions and signaling pathways. Key findings were validated using independent datasets and protein expression data from the Human Protein Atlas.

RESULTS

Calcitriol treatment reduced proliferative cell populations and highlighted the FoxO signaling pathway's role in DKD. and were identified as key markers linked to immune infiltration and renal function. These genes were significantly associated with creatinine levels and eGFR, indicating their potential role in DKD progression.

CONCLUSION

Our results suggest that calcitriol modulates DKD fibrosis through the FoxO pathway, with and serving as potential biomarkers for kidney protection. These results provide fresh insights into strategies for treating DKD.