322 Down-regulation of mir-10a induces il-8 in human mesangial cells stimulated with anti-dsdna igg antibodies

Background and aims The objective of this study is to investigate the role of miRNA in human mesangial cells (HMCs) stimulated with anti-dsDNA IgG antibodies. Methods The HMCs were treated with anti-dsDNA IgG antibodies purified from active systemic lupus erythematosus patients or IgG controls in the presence of normal serum for 3 hours. The small RNA expression profile was screened using high throughput sequencing. Results The results showed that anti-dsDNA IgG up-regulated 103 miRNAs and down-regulated 20 miRNAs which regulate cell cycle, catabolic process, regulation of transcription and apoptosis pathways. Interestingly, miR-10a in HMCs could be validated as specifically down-regulated in HMCs by anti-dsDNA IgG stimulation. The miR-10a was downregulated in kidney biopsies from lupus nephritis patients and correlated with proteinuria Transiently miR-10a knockdown HMCs increased cells proliferation and up-regulated IL-8 expression. The luciferase assay confirmed that miR-10a down-regulated IL-8 expression by complementary binding to 3’UTR in IL-8. Conclusions In conclusion, anti-dsDNA IgG Ab down-regulated miR-10a expression in HMC resulting in the induction of various target genes involved in HMCs proliferation as well as inflammation. Manipulation of miR-10a might be a new option for targeted therapy for lupus nephritis.