MiR-155 in the progression of lung fibrosis in systemic sclerosis. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Christmann, Romy; Wooten, Alicia; Sampaio-Barros, Percival; Borges, Claudia; Carvalho, Carlos; Kairalla, Ronaldo; Feghali-Bostwick, Carol; Ziemek, Jessica; Mei, Yu; Goummih, Salma; Tan, Jiangning; Alvarez, Diana; Kass, Daniel; Rojas, Mauricio; de Mattos, Thiago; Parra, Edwin; Stifano, Giuseppina; Capelozzi, Vera; Simms, Robert; Lafyatis, Robert
• Is Part Of: Arthritis research & therapy. Volume 18:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Systemic Sclerosis -- Lung fibrosis -- Gene expression -- microRNA -- Biomarker -- miR-155 -- Bleomycin; Arthritis -- Periodicals; Arthritis -- Treatment -- Periodicals; 616.722005
• DOI: 10.1186/s13075-016-1054-6
• Languages: English
• ISSNs: 1478-6362

Abstract

Abstract Background MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. Methods RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2–3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.