Evaluation of serum miR-122-5p, miR-486-5p, miR-21-5p, and their interplay with inflammatory markers in diabetic nephropathy: a case control study

The development of diabetic kidney disease (DKD), a major consequence of type 2 diabetes mellitus (T2DM), is impacted by hereditary factors, immunological dysregulation, and inflammation. Inflammatory indicators and circulating microRNAs (miRNAs) can be stable and used as diagnostic biomarkers. The objective of this study was to assess whether serum miRNA-122-5p, miRNA-486-5p, and miRNA-21-5p can serve as non-invasive diagnostic biomarkers for DKD by comparing their levels in T2DM patients with and without DKD against healthy controls, and by examining their correlations with inflammatory markers (IL-6, TNF-α, and hsCRP). Finally, their role in DKD pathogenesis was also investigated through their possible target genes using a bioinformatic analysis. A total of 1350 individuals were enrolled: 450 T2DM with DKD, 450 with T2DM without DKD, and 450 healthy controls. We used qRT-PCR to quantify miRNA expression, ELISA to assess IL-6 and TNF-α, and an immunoturbidimetric technique to detect hsCRP. We found that miRNA-122-5p and miRNA-21-5p levels were substantially elevated in DKD patients and positively correlated with hsCRP and TNF-α; miRNA-21-5p also correlated with IL-6. Conversely, miRNA-486-5p expression was markedly reduced in the DKD group and showed no correlation with inflammatory markers. Enrichment analysis revealed involvement in TNF signaling, insulin resistance, and growth hormone pathways. Their differential expression in DKD may support the utility of miRNA-122-5p, miRNA-21-5p, and miRNA-486-5p expression as potential biomarkers for DKD.