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Association of elevated urinary miR-126, miR-155, and miR-29b with diabetic kidney disease

Beltrami, Cristina, Simpson, Kate, Jesky, Mark, Wonnacott, Alexa, Carrington, Christopher, Holmans, Peter, Newbury, Lucy, Jenkins, Robert, Ashdown, Thomas, Dayan, Colin, Satchell, Simon, Corish, Peter, Cockwell, Paul, Fraser, Donald and Bowen, Timothy 2018. Association of elevated urinary miR-126, miR-155, and miR-29b with diabetic kidney disease. American Journal of Pathology 188 (9) , pp. 1982-1992. 10.1016/j.ajpath.2018.06.006

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Abstract

Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary miRNAs represent a potential source of novel noninvasive 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 with 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 increase; P < 0.001), and miR-29b (4.6-fold increase; 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 with 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsy specimens, followed by quantitative RT-PCR, detected miR-155 in glomeruli and 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 with podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumor necrosis factor-α and transforming growth factor-β1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Cardiff Institute Tissue Engineering Repair (CITER)
Publisher: Elsevier
ISSN: 0002-9440
Date of First Compliant Deposit: 6 July 2018
Date of Acceptance: 11 June 2018
Last Modified: 27 Jul 2020 14:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/113007

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