title: miR-155 in the progression of lung fibrosis in systemic sclerosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA. romy.souza@gmail.com.
authors.forename: Romy B
authors.initials: RB
authors.lastname: Christmann
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wooten
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Percival
authors.initials: P
authors.lastname: Sampaio-Barros
authors.affiliation: Universidade CEUMA, São Luís do Maranhão, MA, Brazil.
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Borges
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carlos R R
authors.initials: CR
authors.lastname: Carvalho
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Kairalla
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Feghali-Bostwick
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ziemek
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Salma
authors.initials: S
authors.lastname: Goummih
authors.affiliation: University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care Medicine, and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pittsburgh, PA, USA.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Tan
authors.affiliation: University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care Medicine, and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pittsburgh, PA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Alvarez
authors.affiliation: University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care Medicine, and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pittsburgh, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kass
authors.affiliation: University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care Medicine, and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pittsburgh, PA, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Universidade do Estado do Amazonas, Manaus, AM, Brazil.
authors.forename: Thiago Lemos
authors.initials: TL
authors.lastname: de Mattos
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Edwin
authors.initials: E
authors.lastname: Parra
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Stifano
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simms
authors.affiliation: Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA.|University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care Medicine, and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pittsburgh, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000150:complications*
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Bleomycin; Gene expression; Lung fibrosis; Systemic Sclerosis; miR-155; microRNA