Association of Elevated Urinary miR-126, miR-155, and miR-29b with Diabetic Kidney Disease

Abstract

Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary miRNAs represent a potential source of novel noninvasive disease sentinels. We profiled 754 miRNAs in pooled urine samples from DKD patients (n = 20), detecting significantly increased miR-126, miR-155, and miR-29b compared with controls (n = 20). These results were confirmed in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD, and 41 controls: miR-126 (2.8-fold increase; P < 0.0001), miR-155 (1.8-fold increase; P < 0.001), and miR-29b (4.6-fold increase; P = 0.024). Combined receiver operating characteristic curve analysis resulted in an area under the curve of 0.8. A relative quantification threshold equivalent to 80% sensitivity for each miRNA gave a positive signal for 48% of DKD patients compared with 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsy specimens, followed by quantitative RT-PCR, detected miR-155 in glomeruli and proximal and distal tubules, whereas miR-126 and miR-29b were most abundant in glomerular extracts. Subsequent experiments showed miR-126 and miR-29b enrichment in glomerular endothelial cells (GEnCs) compared with podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumor necrosis factor-α and transforming growth factor-β1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs.

Urinary exosomes: Potential biomarkers for diabetic nephropathy

“…5 An interesting approach for therapeutic intervention in diabetes would be cell-specific delivery of these molecules. Urine is an attractive source of molecular markers for DN [6][7][8][9][10][11][12][13] (Table 1). Urine miRNA levels might be reflective of the intrinsic kidney tissue injury.…”

The potential of microRNA‐126 in predicting disease risk, mortality of sepsis, and its correlation with inflammation and sepsis severity

“…miR‐126 regulates gene transcription, translation, and degradation of mRNAs, which has been researched regarding its role in the pathogenesis of inflammation, autoimmunity, and organ failures. For instance, high miR‐126 level is associated with the development of kidney injury in diabetic patients and chronic kidney disease patients 6,7 . Furthermore, miR‐126 participates in the pathogenesis of active ulcerative colitis via regulating NF‐kappa B inhibitor (Iκ‐Bα) 8,9 .…”

Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy

“…MicroRNAs (miRNAs) regulate the expression of target genes [ 15 ]. Previous studies showed that the expression level of miR-155 was downregulated in tissues and urine samples of DN patients [ 16 , 17 ]. The abnormal expression of miR-155-5p in DN patients may be related to the disease stage of patients or the pathogenesis of DN [ 17 ].…”