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

Beltrami, Cristina, Simpson, Kate, Jesky, Mark, Wonnacott, Alexa ORCID: https://orcid.org/0000-0002-0968-4248, Carrington, Christopher, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, Newbury, Lucy, Jenkins, Robert ORCID: https://orcid.org/0000-0001-8500-9044, Ashdown, Thomas, Dayan, Colin ORCID: https://orcid.org/0000-0002-6557-3462, Satchell, Simon, Corish, Peter, Cockwell, Paul, Fraser, Donald ORCID: https://orcid.org/0000-0003-0102-9342 and Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435 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:	05 Jan 2024 06:44
URI:	https://orca.cardiff.ac.uk/id/eprint/113007

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