Identifying cell enriched miRNAs in kidney injury and repair

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.