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

著者 Beltrami C , Simpson K , Jesky M , Wonnacott A , Carrington C , Holmans P , Newbury L , Jenkins R , Ashdown T , Dayan C , Satchell S , Corish P , Cockwell P , Fraser D , Bowen T
Am J Pathol.2018 Jul 05 ; ():.
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Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary microRNAs (miRNAs) represent a potential source of novel non-invasive 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 to 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; P < 0.001), and miR-29b (4.6-fold; 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 to 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsies followed by RT-qPCR detected miR-155 in glomeruli, 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 to podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumour necrosis factor-alpha and transforming growth factor-beta 1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs.
PMID: 29981742 [PubMed - as supplied by publisher]
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