title: miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy.
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.
  
  
  CONCLUSIONS
  These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN.
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Zongji
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000419:Albuminuria / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000652:urine*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000652:urine*; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D012372:ROC Curve; D053773:Transforming Growth Factor beta1 / Q000652:urine*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C546783:MIRN192 microRNA, human; C554846:MIRN194 microRNA, human; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D003404:Creatinine