MiR-130b ameliorates murine lupus nephritis through targeting type I interferon pathway on resident renal cells.

Type I Interferon (IFN) is a critical pathogenic factor during the progression of Lupus Nephritis (LN). Although microRNAs (miRNAs) have been shown to control IFN response in immune cells of LN, the role of miRNAs in resident renal cells remain unclear. Here, we investigated the role of miR-130b in IFN pathway in renal cells, and its therapeutic effect in LN.
Kidney tissues from patients and mouse model of LN were collected for detecting miR-130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR-130b in IFN pathway. We overexpressed miR-130b by administrating miR-130b agomir in an IFNα-accelerated LN mouse model to test its therapeutic efficacy.
Downregulated miR-130b expression was observed in kidney tissues from patients and mouse model of LN. Further analysis showed that underexpression of miR-130b negatively correlated with abnormal activation of IFN response in LN patients. In vitro, overexpressing miR-130b suppressed the downstream of type I IFN pathway in RMCs by targeting interferon regulatory factor 1 (IRF1). The opposite effect was observed when inhibited internal miR-130b expression. The inverse correlation between IRF1 and miR-130b levels was detected in renal biopsies from LN patients. More importantly, in vivo administration of miR-130b agomir reduced IFNα-accelerated LN progression, including decreased proteinuria, lower levels of complexes deposition and lack of glomeruli lesion.
miR-130b is a novel negative regulator of type I IFN pathway in renal cells. Overexpression of miR-130b in vivo ameliorates IFNα-accelerated LN, providing potential novel strategies for LN therapeutic intervention. This article is protected by copyright. All rights reserved.
© 2016, American College of Rheumatology.

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