Universität zu Köln

Pawluczyk, Izabella Z. A., Didangelos, Athanasios, Barbour, Sean J., Er, Lee, Becker, Jan U., Martin, Roberto, Taylor, Scott, Bhachu, Jasraj S., Lyons, Edward G., Jenkins, Robert H., Fraser, Donald, Molyneux, Karen, Perales-Paton, Javier ORCID: 0000-0003-0780-6683, Saez-Rodriguez, Julio ORCID: 0000-0002-8552-8976 and Barratt, Jonathan ORCID: 0000-0002-9063-7229 (2021). Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression. Kidney Int., 99 (5). S. 1127 - 1140. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal kidney function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of kidney biopsies in order to identify microRNAs specifically associated with the risk of IgA nephropathy progression. Following sequencing and validation in independent cohorts, four microRNAs (-1505p,-155-5p, -146b-5p, -135a-5p) were found to be differentially expressed in IgA nephropathy progressors compared to non-progressors, and patients with thin membrane nephropathy, lupus nephritis and membranous nephropathy, and correlated with estimated glomerular filtration rate, proteinuria, and the Oxford MEST-C scores (five histological features that are independent predictors of clinical outcome). Each individual microRNA increased the discrimination score of the International IgAN Prediction Tool, although due to the small number of samples the results did not reach statistical significance. miR-150-5p exhibited the largest amplitude of expression between cohorts and displayed the best discrimination between IgA nephropathy progressors and nonprogressors by receiver operating curve analysis (AUC: 0.8). However, expression was similarly upregulated in kidneys with established fibrosis and low estimated glomerular filtration rates at the time of biopsy. Consistent with a more generic role in kidney fibrosis, in situ hybridization revealed that miR-150-5p was found in lymphoid infiltrates, and areas of proliferation and fibrosis consistent with the known drivers of progression. Thus, miR-150-5p may be a potential functional mediator of kidney fibrosis that may add value in predicting risk of progression in IgA nephropathy and other kidney diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pawluczyk, Izabella Z. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Didangelos, Athanasios UNSPECIFIED UNSPECIFIED UNSPECIFIED Barbour, Sean J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Er, Lee UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Roberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Taylor, Scott UNSPECIFIED UNSPECIFIED UNSPECIFIED Bhachu, Jasraj S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lyons, Edward G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenkins, Robert H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fraser, Donald UNSPECIFIED UNSPECIFIED UNSPECIFIED Molyneux, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Perales-Paton, Javier UNSPECIFIED orcid.org/0000-0003-0780-6683 UNSPECIFIED Saez-Rodriguez, Julio UNSPECIFIED orcid.org/0000-0002-8552-8976 UNSPECIFIED Barratt, Jonathan UNSPECIFIED orcid.org/0000-0002-9063-7229 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-595289
DOI:	10.1016/j.kint.2020.12.028
Journal or Publication Title:	Kidney Int.
Volume:	99
Number:	5
Page Range:	S. 1127 - 1140
Date:	2021
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PARIETAL EPITHELIAL-CELLS; T-CELLS; LYMPHOCYTES Multiple languages Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59528