MicroRNA-10a regulation of proinflammatory mediators: An important component of untreated juvenile dermatomyositis

Dong Xu, Chiang Ching Huang, Akadia Kachaochana, Gabrielle A. Morgan, Maria F. Bonaldo, Marcelo B. Soares, Fabricio Costa, John Sarwark, Simone T. Sredni, Lauren M. Pachman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective. To identify differentially expressed microRNA (miRNA) in muscle biopsies (MBx) from 15 untreated children with juvenile dermatomyositis (JDM) compared with 5 controls. Methods. Following MBx miRNA profiling, differentially expressed miRNA and their protein targets were validated by quantitative real-time PCR (qRT-PCR) and immunological assay. The association of miRNA-10a and miRNA-10b with clinical data was evaluated, including Disease Activity Score (DAS), von Willebrand factor antigen (vWF:Ag), nailfold capillary end row loops, duration of untreated disease, and tumor necrosis factor (TNF)-α-308A allele. Results. In JDM, 16/362 miRNA were significantly differentially expressed [false discovery rate (FDR) < 0.05]. Among these, miRNA-10a was the most downregulated miRNA in both FDR and ranking of fold change: miRNA-10a = -2.27-fold, miRNA-10b = -1.80-fold. Decreased miRNA-10a and miRNA-10b expressions were confirmed using qRT-PCR: -4.16 and -2.59 fold, respectively. The qRT-PCR documented that decreased miRNA-10a expression was related to increased vascular cell adhesion molecule 1 in 13 of these JDM cases (correlation -0.67, p = 0.012), unlike miRNA-10b data (not significant). Concurrent JDM plasma contained increased levels of interleukin (IL) 6 (p = 0.0363), IL-8 (p = 0.0005), TNF-α (p = 0.0011), and monocyte chemoattractant proteins 1 (p = 0.0139). Decreased miRNA-10a, but not miRNA-10b, was associated with the TNF-α-308A allele (p = 0.015). In the 15 JDM, a trend of association of miRNA-10a (but not miRNA-10b) with vWF:Ag and DAS was observed. Conclusion. MiRNA-10a downregulation is an important element in untreated JDM muscle pathophysiology. We speculate that muscle miRNA expression in adult dermatomyositis differs from muscle miRNA expression in untreated childhood JDM.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalJournal of Rheumatology
Volume43
Issue number1
DOIs
StatePublished - Jan 2016

Keywords

  • Inflammatory cytokines
  • Juvenile dermatomyositis
  • MicroRNA microarray
  • MicroRNA-10

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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