MicroRNA-10a Regulation of Proinflammatory Mediators: An Important Component of Untreated Juvenile Dermatomyositis

• Published in: Journal of rheumatology 2016-01, Vol.43 (1), p.161-168
• Main Authors: Xu, Dong, Huang, Chiang-Ching, Kachaochana, Akadia, Morgan, Gabrielle A, Bonaldo, Maria F, Soares, Marcelo B, Costa, Fabricio, Sarwark, John, Sredni, Simone T, Pachman, Lauren M
• Format: Article
• Language: English
• Subjects: Biopsy, Needle; Case-Control Studies; Child; Child, Preschool; Cytokines - metabolism; Dermatomyositis - genetics; Dermatomyositis - pathology; Dermatomyositis - therapy; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation - immunology; Humans; Image-Guided Biopsy; Immunohistochemistry; Inflammation Mediators - metabolism; Magnetic Resonance Imaging - methods; Male; MicroRNAs - genetics; Real-Time Polymerase Chain Reaction - methods; Reference Values; Sampling Studies; Severity of Illness Index
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.141474

To identify differentially expressed microRNA (miRNA) in muscle biopsies (MBx) from 15 untreated children with juvenile dermatomyositis (JDM) compared with 5 controls. 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. 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 q -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. 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.