Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression
Autor: | Donald James Fraser, Jasraj S. Bhachu, Scott Taylor, Sean J. Barbour, Robert H. Jenkins, Karen Molyneux, Izabella Z.A. Pawluczyk, Jan U. Becker, Julio Saez-Rodriguez, Athanasios Didangelos, Edward G. Lyons, Jonathan Barratt, Javier Perales-Patón, Lee Er, Roberto Martin |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
030232 urology & nephrology Lupus nephritis Renal function Kidney Nephropathy 03 medical and health sciences 0302 clinical medicine Membranous nephropathy Fibrosis Biopsy medicine Humans Proteinuria medicine.diagnostic_test business.industry Glomerulonephritis IGA medicine.disease MicroRNAs 030104 developmental biology medicine.anatomical_structure Nephrology Immunology Disease Progression medicine.symptom business Biomarkers Glomerular Filtration Rate |
Zdroj: | Kidney international. 99(5) |
ISSN: | 1523-1755 |
Popis: | 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 (-150-5p, -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 non-progressors 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. |
Databáze: | OpenAIRE |
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