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Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus
Javier Perez-Hernandez1, Maria J Forner2, Carolina Pinto2
1Genotyping and Genetic Diagnosis Unit, INCLIVA Biomedical Research Institute, Valencia, Spain; Cardiometabolic and Renal Unit, INCLIVA Biomedical Research Institute, Valencia, Spain.
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.
Insights
Urinary microRNAs (miRNAs) are mainly in exosomes for systemic lupus erythematosus patients. Active lupus nephritis significantly increases exosomal miR-146a, suggesting potential as a non-invasive renal disease biomarker.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRNAs) are increasingly recognized as potential biomarkers for various diseases.
- The localization of miRNAs in body fluids, particularly within exosomes, remains a subject of investigation.
Purpose of the Study:
- To determine if urinary miRNAs are concentrated within exosomes.
- To investigate how systemic lupus erythematosus (SLE) and lupus nephritis affect urinary miRNA distribution patterns.
Main Methods:
- Quantitative reverse-transcription PCR was used to measure specific miRNAs in urine samples.
- Urine was fractionated into cell-free urine, exosome-depleted supernatant, and exosome pellet via ultracentrifugation.
- Samples from SLE patients (n=38) and healthy controls (n=12) were analyzed.
Main Results:
- In healthy controls, specific miRNAs showed differential distribution between exosomes and supernatant.
- In SLE patients, all tested urinary miRNAs were predominantly found within exosomes.
- Active lupus nephritis patients exhibited a significant increase in exosomal miR-146a (100-fold change), distinguishing them from controls and SLE patients without nephritis.
Conclusions:
- Urinary miRNAs in SLE are primarily exosome-enclosed.
- Exosomal miR-146a levels are significantly elevated in active lupus nephritis.
- Urinary exosomal miRNAs represent a promising, non-invasive biomarker for renal disease in SLE.
