Beltrami, Cristina, Simpson, Kate, Jesky, Mark, Wonnacott, Alexa ![]() ![]() ![]() ![]() ![]() ![]() |
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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 |
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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: | 05 Jan 2024 06:44 |
URI: | https://orca.cardiff.ac.uk/id/eprint/113007 |
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