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

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Diabetic nephropathy (DKD) is a leading cause of advanced renal failure with limited therapeutic options.
• Calcitriol demonstrates potential for treating DKD-related fibrosis, but its underlying molecular mechanisms require elucidation.
• Understanding calcitriol's effects on DKD fibrosis is crucial for developing novel treatment strategies.

Purpose of the Study:

• To identify key genes and signaling pathways affected by calcitriol in the context of DKD-related fibrosis.
• To investigate the molecular mechanisms through which calcitriol exerts its antifibrotic effects in DKD.
• To explore potential biomarkers for monitoring DKD progression and calcitriol's therapeutic efficacy.

Main Methods:

• Single-cell gene expression profiling of calcitriol-treated DKD rat kidney tissue.
• Analysis of fibrosis-associated cell subsets and gene-immune cell interactions using Mendelian randomization and enrichment analyses (CIBERSORT, GSVA, GSEA, Motif Enrichment).
• Validation of key findings using independent datasets and human protein expression data.

Main Results:

• Calcitriol treatment led to a reduction in proliferative cell populations in DKD kidney tissue.
• The FoxO signaling pathway was identified as a key player modulated by calcitriol in DKD.
• SUMO3 and CD74 emerged as significant markers associated with immune infiltration, renal function (creatinine levels, eGFR), and DKD progression.

Conclusions:

• Calcitriol modulates DKD fibrosis via the FoxO signaling pathway.
• SUMO3 and CD74 represent potential biomarkers for kidney protection in DKD.
• This study offers novel insights into calcitriol-based therapeutic strategies for diabetic kidney disease.