Abstract
Background. miR-192, miR-194, and miR-215 are enriched in the kidney and play roles in the pathogenesis of diabetic nephropathy (DN). Extracellular vesicles (EVs) can be detected in body fluids and may serve as disease biomarkers. Methods. Eighty type 2 diabetes patients with normoalbuminuria (n = 30), microalbuminuria (n = 30), or macroalbuminuria (n = 20), as well as 10 healthy controls, were enrolled in this study. Real-time PCR was used to evaluate urinary EV miRNAs expression. Results. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. In patients with normoalbuminuria and microalbuminuria, miR-192 was positively correlated with albuminuria (r = 0.357, P = 0.005) levels and transforming growth factor- (TGF-) β1 (r = 0.356, P = 0.005) expression. Receiver operating characteristic (ROC) curve analysis revealed that miR-192 was better than miR-194 and miR-215 in discriminating the normoalbuminuric group from the microalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. Conclusion. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN.
Highlights
Diabetic nephropathy (DN) occurs in over 30% of patients with type 2 diabetes mellitus (T2DM) and is the main cause of end-stage renal disease (ESRD) [1]
MicroRNAs are a group of short (∼21 nucleotides) noncoding RNAs that are critically involved in many biological processes and may serve as potential biomarkers of several diseases due to their specificity and stability in body fluids [5, 6]. miR-192, miR-194, and miR-215 have been reported to be highly expressed in kidney tissue and play critical roles in kidney development and differentiation [7]. miR-215 and miR-194-1 are located on the same chromosome, as are miR-192 and miR-194-2. miR-192 and miR-215 share the same seed sequence, and miR-194-1 and miR-194-2 possess the same mature sequence [8]. miR-192 and miR-215 have been shown to be dramatically upregulated and are involved in promoting renal glomerular and tubulointerstitial fibrosis in diabetic nephropathy (DN) [9]
Previous studies have reported that urinary miRNAs are primarily detected in exosomes, and changes in miRNAs are significant in exosomes relative to other urine fractions [26], indicating that exosomal RNA in urine may serve as a potential renal disease marker
Summary
Diabetic nephropathy (DN) occurs in over 30% of patients with type 2 diabetes mellitus (T2DM) and is the main cause of end-stage renal disease (ESRD) [1]. MicroRNAs (miRNAs) are a group of short (∼21 nucleotides) noncoding RNAs that are critically involved in many biological processes and may serve as potential biomarkers of several diseases due to their specificity and stability in body fluids [5, 6]. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN
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