miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy.
miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy.
复制标题
尿液细胞外囊泡中的 miRNA 作为早期糖尿病肾病的预测因子
DOI：
10.1155/2016/7932765
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Jia Y;Guan M;Zheng Z;Zhang Q;Tang C;Xu W;Xiao Z;Wang L;Xue Y
背景。 miR-192、miR-194 和 miR-215 在肾脏中富集，在糖尿病肾病 (DN) 的发病机制中发挥作用。细胞外囊泡（EV）可以在体液中检测到，并可以作为疾病生物标志物。方法。本研究纳入了 80 名正常白蛋白尿 (n = 30)、微量白蛋白尿 (n = 30) 或大量白蛋白尿 (n = 20) 的 2 型糖尿病患者以及 10 名健康对照者。使用实时 PCR 评估尿 EV miRNA 的表达。结果。尿液 EV 中 miR-192 水平显着高于 miR-194 和 miR-215 水平，并且与正常白蛋白尿组和对照受试者相比，微量白蛋白尿组中所有三种 miRNA 均显着增加，但在大量白蛋白尿组中均下降。在白蛋白尿和微量白蛋白尿正常的患者中，miR-192与白蛋白尿（r = 0.357，P = 0.005）水平和转化生长因子-（TGF-）β1（r = 0.356，P = 0.005）表达呈正相关。受试者工作特征（ROC）曲线分析显示，miR-192 在区分正常白蛋白尿组和微量白蛋白尿组方面优于 miR-194 和 miR-215。将人肾小管上皮细胞暴露于高葡萄糖会增加细胞上清液 EV 中两种 miRNA 的表达，表明存在潜在来源。结论。这些结果表明尿液 EV miR-192 作为 DN 早期生物标志物的潜在用途。
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.