Identifying cell-enriched miRNAs in kidney injury and repair
| Autor: | Julie Rodor, Stephen J. Wigmore, Oliver Teenan, Caroline O. S. Savage, Riinu Pius, Carolynn Cairns, Jeremy Hughes, Bryan R. Conway, Robert B Henderson, Sarah Finnie, Katie Connor, Vishal Sahni, Lorna P. Marson, Gillian M Tannahill, Laura Denby, Ewen M Harrison, Victoria Banwell, Rachel Thomas |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Nephrology Male medicine.medical_specialty Bioinformatics Noncoding RNAs Renal cortex Cell lcsh:Medicine Biology Kidney Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Internal medicine microRNA medicine Animals Organ transplantation Gene Expression Profiling Macrophages lcsh:R Acute kidney injury Computational Biology Endothelial Cells High-Throughput Nucleotide Sequencing General Medicine Acute Kidney Injury medicine.disease Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure Kidney Tubules Organ Specificity 030220 oncology & carcinogenesis Cancer research Medicine DNA microarray Biomarkers Kidney disease Research Article |
| Zdroj: | JCI Insight JCI Insight, Vol 5, Iss 24 (2020) Connor, K L, Teenan, O, Cairns, C, Banwell, V, Thomas, R A B, Rodor, J, Finnie, S, Pius, R, Tannahill, G M, Sahni, V, Savage, C O S, Hughes, J, Harrison, E M, Henderson, R B, Marson, L P, Conway, B R, Wigmore, S J & Denby, L 2020, ' Identifying cell enriched miRNAs in kidney injury and repair ', JCI Insight, vol. 5, no. 24, e140399 . https://doi.org/10.1172/jci.insight.140399 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.140399 |
| Popis: | Small noncoding RNA, microRNAs (miRNAs), are emerging as important modulators in the pathogenesis of kidney disease, with potential as biomarkers of kidney disease onset, progression or possibly outcome from treatment. Bulk tissue small RNA-Sequencing (sRNA-seq) and microarrays are widely used to identify dysregulated miRNA expression but are limited by the lack of precision regarding the cellular origin of the miRNA. In this study, we performed cell-specific sRNA-seq on tubular cells, endothelial cells, fibroblasts and macrophages isolated from the injured and repairing kidneys of the murine reversible unilateral ureteric obstruction model. We devised an unbiased bioinformatics pipeline to define the miRNA enrichment within these cell populations, constructing a miRNA catalogue of injury and repair. Our analysis reveals that a significant proportion of cell-specific miRNAs in healthy animals were no longer specific following injury. We then apply this knowledge of the relative cell specificity of miRNAs to deconvolute bulk miRNA expression changes in kidney disease from murine models and human renal disease kidney samples comprised of mixed cell types. Finally, we use our data-driven approach to rationally select and demonstrate macrophage enriched miR-16-5p and miR-18a as promising urinary biomarkers of acute kidney injury in renal transplant recipients. |
| Databáze: | OpenAIRE |
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