miR-155 in the progression of lung fibrosis in systemic sclerosis

Autor(es):Mostrar menos -

Christmann, Romy B. ^[1] ; Wooten, Alicia ^[1] ; Sampaio-Barros, Percival ^[2] ; Borges, Claudia L. ^[3] ; Carvalho, Carlos R. R. ^[2] ; Kairalla, Ronaldo A. ^[2] ; Feghali-Bostwick, Carol ^[4] ; Ziemek, Jessica ^[1] ; Mei, Yu ^[1] ; Goummih, Salma ^[1] ; Tan, Jiangning ^{[5, 6]} ; Alvarez, Diana ^{[5, 6]} ; Kass, Daniel J. ^{[5, 6]} ; Rojas, Mauricio ^{[5, 6]} ; de Mattos, Thiago Lemos ^[7] ; Parra, Edwin ^[2] ; Stifano, Giuseppina ^[1] ; Capelozzi, Vera L. ^[2] ; Simms, Robert W. ^[1] ; Lafyatis, Robert ^{[1, 5, 6]}

Afiliação do(s) autor(es)

^[1] Boston Univ, Sch Med, Arthrit Ctr, E501, Med Campus, 72 East Concord St, Boston, MA 02118 - USA

^[2] Univ Sao Paulo, Hosp Clin, Fac Med, Sao Paulo, SP - Brazil

^[3] Univ CEUMA, Sao Luis Do Maranhao, MA - Brazil

^[4] Med Univ South Carolina, Charleston, SC 29425 - USA

^[5] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA - USA

^[6] Dorothy P & Richard P Simmons Ctr Interstitial Lu, Pittsburgh, PA - USA

^[7] Univ Estado Amazonas, Manaus, Amazonas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARTHRITIS RESEARCH & THERAPY; v. 18, JUL 5 2016.
• Citações Web of Science: 47

Resumo

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. (AU)

• Processo FAPESP: 13/14277-4 - Prognóstico e evolução clínica de novos e vigentes biomarcadores genéticos e protéicos em câncer de pulmão
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Regular