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

Background and aimsThe objective of this study is to investigate the role of miRNA in human mesangial cells (HMCs) stimulated with anti-dsDNA IgG antibodies.MethodsThe HMCs were treated with anti-dsDNA IgG antibodies purified from active systemic lupus erythematosus patients or IgG controls in the p...

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Bibliographic Details
Published in:	Lupus science & medicine Vol. 4; no. Suppl 1; p. A144
Main Authors:	Tangtanatakul, P, Thammasate, B, Jacquet, A, Reantragoon, R, Pisitkun, T, Avihingsanon, Y, Leelahavanichkul, A, Hirankarn, N
Format:	Journal Article
Language:	English
Published:	London BMJ Publishing Group LTD 01-03-2017
Online Access:	Get full text
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Summary:	Background and aimsThe objective of this study is to investigate the role of miRNA in human mesangial cells (HMCs) stimulated with anti-dsDNA IgG antibodies.MethodsThe 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.ResultsThe 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.ConclusionsIn 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.
ISSN:	2053-8790
DOI:	10.1136/lupus-2017-000215.322