Introduction: MicroRNAs (miRNAS) are responsible for post-transcriptional gene silencing. Our hypothesis is that dysregulated miRNAs modify gene expression programs in lupus nephritis (LN), leading to sustained pathology. Methods: RNA was extracted from 18 kidney specimens of LN patients and 6 controls, human kidney cell lines and primary monocytes. Direct digital detection of over 700 miRNAs was performed and confirmed by qRT-PCR. Results: A LN-specific miRNA signature was identified, reflecting cell proliferation and inflammation, according to pathway analysis. When compared to normal tissue, a significant decrease in miR-26a and miR-30b was found in LN (p=0.002; p=0.005, respectively). The results were confirmed by qRT-PCR. miR-26a was associated with crescents in kidney specimens, a classic proliferative sign (p=0.04). Human kidney tubular, mesangial and endothelial cells expressed miR-26a and miR-30b. These miRNAs were increased in primary monocytes from lupus patients and in monocytes exposed to immune complexes, a stimulus for terminal differentiation. Conclusions: We identified, for the first time, decreased miR-26a and miR-30b expression in LN. These miRNAs have been implicated in the regulation of proliferation and our finding of an association with crescents and increased expression in monocytes from lupus patients, which are known to be more differentiated and more prone to apoptosis, is consistent with a role in the regulation of pathologic proliferation in LN.
- Copyright © 2013 by The American Association of Immunologists, Inc.