TY - JOUR T1 - MicroRNA-10a Regulation of Proinflammatory Mediators: An Important Component of Untreated Juvenile Dermatomyositis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.141474 SP - jrheum.141474 AU - Dong Xu AU - Chiang-Ching Huang AU - Akadia Kachaochana AU - Gabrielle A. Morgan AU - Maria F. Bonaldo AU - Marcelo B. Soares AU - Fabricio Costa AU - John Sarwark AU - Simone T. Sredni AU - Lauren M. Pachman Y1 - 2015/12/01 UR - http://www.jrheum.org/content/early/2015/11/25/jrheum.141474.abstract N2 - 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. ER -