Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension

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.

Exploration of Serum Exosomal LncRNA TBILA and AGAP2-AS1 as Promising Biomarkers for Diagnosis of Non-Small Cell Lung Cancer

“…Great deals of reports have indicated that exosomes-mediated transfer of molecular constituents remodels the tumor microenvironment and contributes to carcinogenesis [10,11]. Notably, exosomes are often found in various human body fluids, including peripheral blood (serum/plasma), urine and saliva [12,13]. Moreover, the exosomal membrane could protect various types of molecules from enzymatic degradation in circulation [14].…”

New insight into the role of extracellular vesicles in kidney disease

“…Interestingly, miRNAs were extremely enriched in the urinary exosome subpopulation, but not MVs in hypertensive patients. Low exosomal miR‐146a was associated with the presence of albuminuria . MiR‐29c from urinary exosome was significantly reduced in CKD patients and inversely correlated with renal fibrosis scores .…”

“…Low exosomal miR-146a was associated with the presence of albuminuria. 75 MiR-29c from urinary exosome was significantly reduced in CKD patients and inversely correlated with renal fibrosis scores. 76 Besides, the diagnostic potential of exosomal miRNA has also been demonstrated in autosomal dominant polycystic kidney disease (ADPKD), streptozotocin (STZ)-induced diabetic nephropathy animal models, patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).…”

Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases

“…In this regard, the urinary exosome has been reported to be a novel biomarker for renal disease [207][208][209]. Moreover, the stability and enrichment of miRNA in the exosome make it a promising candidate as a biomarker for different glomerular diseases [210][211][212][213][214][215]. However, recent studies have indicated that exosomes derived from glomerular cells such as podocytes may not be regarded only as an indicator of glomerular status.…”