Abstract

Background: Diabetic kidney disease has substantial burden and limited therapeutic options. An inadequate understanding of the complex gene regulatory circuits underlying this disorder contributes to the insufficiency of current treatment strategies. MicroRNAs (miRNAs) play a crucial role as regulators of functionally related gene networks. Previously, mmu-mir-802-5p was identified as the sole dysregulated miRNA in both the kidney cortex and medulla of diabetic mice. This study aims to investigate the role of miR-802-5p in diabetic kidney disease. Materials and Methods: The validated and predicted targets of miR-802-5p were identified using miRTarBase and TargetScan databases, respectively. The functional role of this miRNA was inferred using gene ontology enrichment analysis. The expression of miR-802-5p and its selected targets were assessed by qPCR. The expression of the angiotensin receptor (Agtr1a) was measured by ELISA. Results: miR-802-5p exhibited dysregulation in both the kidney cortex and medulla of diabetic mice, with two- and four-fold over-expressions, respectively. Functional enrichment analysis of the validated and predicted targets of miR-802-5p revealed its involvement in the renin-angiotensin pathway, inflammation, and kidney development. Differential expression was observed in the Pten transcript and Agtr1a protein among the examined gene targets. Conclusion: These findings suggest that miR-802-5p is a critical regulator of diabetic nephropathy in the cortex and medulla compartments, contributing to disease pathogenesis through the renin-angiotensin axis and inflammatory pathways.

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