Abstract
There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.
Highlights
Over the last few years, there has been increasing interest in detecting body fluid micro RNAs as biomarkers of activity in several diseases
Quantification of micro RNAs (miRNAs) demonstrated that intact miRNAs are enriched in exosome-containing pellet compared to cell-free urine (CFU) and Sn of urine, confirming that miRNAs were concentrated inside exosomes, miR146a was slightly higher in CFU rather exosome pellet
These results would be in concordance with a recent publication in other body fluids that found that the majority of miRNAs detectable in human serum and saliva is concentrated in exosomes [36]
Summary
Over the last few years, there has been increasing interest in detecting body fluid micro RNAs (miRNAs) as biomarkers of activity in several diseases. Exosomes are small membrane vesicles with a size of 30–100 nm that are secreted by different cell types [12] They can be isolated from a variety of body fluids, including plasma, urine, saliva, amniotic fluid and breast milk [13,14]. It has been recently reported that exosomes were enriched in miRNA, mRNA, small nuclear RNA, transfer RNA and long intergenic RNA [15,16]. This finding sparked the idea that exosomes may represent a new type of intercellular messenger, playing an important role in cell-to-cell communication, and serve as potential biomarkers for diagnosis, prognosis, or predictive response to therapies
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