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

Cristina Beltrami, Kate Simpson, Mark Jesky, Alexa Wonnacott, Christopher Carrington, Peter Holmans, Lucy Newbury, Robert Jenkins, Thomas Ashdown, Colin Dayan, Simon Satchell, Peter Corish, Paul Cockwell, Donald Fraser, Timothy Bowen*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)
168 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1982-1992
Number of pages11
JournalAmerican Journal of Pathology
Volume188
Issue number9
Early online date6 Jul 2018
DOIs
Publication statusPublished - 2 Sep 2018

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