Abstract
BackgroundThere is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension.MethodsExosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed.ResultsUrinary miRNAs are highly enriched in exosome subpopulations compared to MVs, both in patients with or without increased albuminuria (p < 0.001), but not in the control group. High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p = 0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR-146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001), and discriminated the presence of urinary albumin excretion presence [area under the curve = 0.80, 95% confidence interval: 0.66–0.95; p = 0.0013].ConclusionsOur results indicate that miRNAs were enriched in the urinary exosome subpopulation in hypertensive patients and that low miR-146a expression in exosomes was associated with the presence of albuminuria. Thus, urinary exosome miR-146a may be a potentially useful tool for studying early renal injury in hypertension.
Highlights
There is increasing interest in using extracellular vesicle-derived microRNAs as biomarkers in renal dysfunction and injury
We investigated the selective sorting of miRNA into exosomes and the potential role of urinary exosome miRNAs as novel markers of early lesion in hypertension
Isolation and characterisation of urinary extracellular vesicles To validate the EV purification protocol, we analysed the morphology of the urinary MVs and exosomes by transmission electron microscopy (Fig. 1a, b)
Summary
There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. The aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. The management of hypertension reduces the levels and microRNAs (miRNAs) are small (18–22 nucleotides), non-coding RNA molecules which are post-transcriptional regulators of gene expression [8]. The expression of these molecules is often tissue-restricted, and this fact has led to the idea that miRNA expression may have organ-specific roles [9, 10], and that these miRNAs are delivered to different extracellular biofluids [11].
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