PT - JOURNAL ARTICLE AU - Oana Milas AU - Florica Gadalean AU - Adrian Vlad AU - Victor Dumitrascu AU - Cristina Gluhovschi AU - Gheorghe Gluhovschi AU - Silvia Velciov AU - Roxana Popescu AU - Flaviu Bob AU - Petru Matusz AU - Agneta-Maria Pusztai AU - Octavian M Cretu AU - Alina Secara AU - Anca Simulescu AU - Sorin Ursoniu AU - Daliborca Vlad AU - Ligia Petrica TI - Deregulated profiles of urinary microRNAs may explain podocyte injury and proximal tubule dysfunction in normoalbuminuric patients with type 2 diabetes mellitus AID - 10.1136/jim-2017-000556 DP - 2018 Apr 01 TA - Journal of Investigative Medicine PG - 747--754 VI - 66 IP - 4 4099 - http://hw-f5-jim.highwire.org/content/66/4/747.short 4100 - http://hw-f5-jim.highwire.org/content/66/4/747.full SO - J Investig Med2018 Apr 01; 66 AB - MicroRNAs (miRNAs) are short non-coding RNA species that are important post-transcriptional regulators of gene expression. The aim of the study was to establish a potential explanation of podocyte damage and proximal tubule (PT) dysfunction induced by deregulated miRNAs expression in the course of type 2 diabetes mellitus (DM). A total of 68 patients with type 2 DM and 11 healthy subjects were enrolled in a cross-sectional study and assessed concerning urinary albumin:creatinine ratio (UACR), urinary N-acetyl-β-D-glucosamininidase (NAG), urinary kidney injury molecule-1, urinary nephrin, podocalyxin, synaptopodin, estimated glomerular filtration rate (eGFR), urinary miRNA21, miRNA124, and miRNA192. In univariable regression analysis, miRNA21, miRNA124, and miRNA192 correlated with urinary nephrin, synaptopodin, podocalyxin, NAG, KIM-1, UACR, and eGFR. Multivariable regression analysis yielded models in which miRNA192 correlated with synaptopodin, uNAG, and eGFR (R2=0.902; P<0.0001), miRNA124 correlated with synaptopodin, uNAG, UACR, and eGFR (R2=0.881; P<0.0001), whereas miRNA21 correlated with podocalyxin, uNAG, UACR, and eGFR (R2=0.882; P<0.0001). Urinary miRNA192 expression was downregulated, while urinary miRNA21 and miRNA124 expressions were upregulated. In patients with type 2 DM, there is an association between podocyte injury and PT dysfunction, and miRNA excretion, even in the normoalbuminuria stage. This observation documents a potential role of the urinary profiles of miRNA21, miRNA124, and miRNA192 in early DN. Despite their variability across the segments of the nephron, urinary miRNAs may be considered as a reliable tool for the identification of novel biomarkers in order to characterize the genetic pattern of podocyte damage and PT dysfunction in early DN of type 2 DM.