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322 Down-regulation of mir-10a induces il-8 in human mesangial cells stimulated with anti-dsdna igg antibodies
  1. P Tangtanatakul1,
  2. B Thammasate2,
  3. A Jacquet3,
  4. R Reantragoon2,
  5. T Pisitkun4,
  6. Y Avihingsanon5,
  7. A Leelahavanichkul2 and
  8. N Hirankarn2
  1. 1Chulalongkorn University, Microbiology, Bangkok, Thailand
  2. 2Chulalongkorn, Microbiology, Bangkok, Thailand
  3. 3Chulalongkorn, Research, Bangkok, Thailand
  4. 4Chulalongkorn, Reserach, Bangkok, Thailand
  5. 5Chulalongkorn, Medicine, Bangkok, Thailand

Abstract

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.

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