Detection and transport mechanisms of circulating microRNAs in neurological, cardiac and kidney diseases.

MicroRNAs are small non-coding RNA transcripts that modulate gene expression and translation through target mRNA destabilization and/or inhibition of protein synthesis. Various studies have aimed at elucidation of the role of these small molecules in the regulation of disease activity. Initially, microRNA were believed to merely act as intracellular mediators fine-tuning mRNA translation into proteins. Recently, the first studies have emerged demonstrating that microRNAs are also externalized from cells and transported in body fluids, thereby shuttling genetic information from a donor to a recipient cell. Thus, circulating microRNAs represent attractive non-invasive detectable markers to monitor onset/ progress of diseases. The present article outlines the quantification and biomarker use of microRNAs in various body fluids of patients with cardiac and kidney disease as well as neurological disorders.

Urinary miR-210 as a mediator of acute T-cell mediated rejection in renal allograft recipients.

MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. Circulating miRNAs are remarkably stable in the blood. We tested whether miRNAs are also detectable in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection. We profiled urinary miRNAs of stable transplant patients and transplant patients with acute rejection. The miR-10a, miR-10b and miR-210 were strongly deregulated in urine of the patients with acute rejection. We confirmed these data in urine of a validation cohort of 62 patients with acute rejection, 19 control transplant patients without rejection and 13 stable transplant patients with urinary tract infection by quantitative RT-PCR. The miR-10b and miR-210 were downregulated and miR-10a upregulated in patients with acute rejection compared to controls. Only miR-210 differed between patients with acute rejection when compared to stable transplant patients with urinary tract infection or transplant patients before/after rejection. Low miR-210 levels were associated with higher decline in GFR 1 year after transplantation. Selected miRNAs are strongly altered in urine of the patients with acute renal allograft rejection. The miR-210 levels identify patients with acute rejection and predict long-term kidney function. Urinary miR-210 may thus serve as a novel biomarker of acute kidney rejection.