Down-regulation of let-7a and miR-21 in urine exosomes from lupus nephritis patients during disease flare.

BACKGROUND: The contents of exosomes determine their biological functions and represent a new class of epigenetic modulation of renal cells considering as novel class of biomarker.

OBJECTIVE: Our study aims to investigate the expression of microRNAs (miRNA), including miR-10a/b, let-7a, and miR-21, in urinary exosomes isolated from patients with active lupus nephritis (LN) compared to inactive LN.

METHODS: The exosomes were obtained from long-term follow up LN patients during active and 4 months after treatment (n = 3). The expression of candidate miRNAs was validated in group of LN patients with renal flare (n = 13) and remission stage (n = 18) using qPCR. All exosomes were characterized by NanoSight and western blotting. The correlation between miRNA expressions and kidney functions was studied.

RESULTS: We found that let-7a and miR-21, but not miR-10a/b, were significantly down-regulated in LN patients with active disease compared with inactive disease. Long-term follow-up patients also showed down-regulation of let-7a and miR-21 during disease flare while the expressions were elevated after complete course of treatment. Although the miRNA expressions were not significantly correlated with classical kidney injury markers, negative correlations were found in both protein leakages and glomerular filtration rate.

CONCLUSION: Our result suggested that urinary exosome-associated miRNA, let-7a and miR-21, could be used to guide the clinical stage of LN patients and possibly plays a role in epigenetic regulation of the kidney during the disease. Its expression might be able to use as liquid biopsy, however, validation in large sample size is required to show it significant in clinical implication.