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

Christmann, RB and Wooten, A and Sampaio-Barros, P and Borges, CL and Carlos, CR and Kairalla, RA and Feghali-Bostwick, C and Ziemek, J and Mei, Y and Goummih, S and Tan, J and Alvarez, D and Kass, DJ and Rojas, M and de Mattos, TL and Parra, E and Stifano, G and Capelozzi, VL and Simms, RW and Lafyatis, R (2016) miR-155 in the progression of lung fibrosis in systemic sclerosis. Arthritis Research and Therapy, 18 (1). ISSN 1478-6354

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Abstract

© 2016 The Author(s). 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Christmann, RB
Wooten, A
Sampaio-Barros, P
Borges, CL
Carlos, CR
Kairalla, RA
Feghali-Bostwick, C
Ziemek, J
Mei, Y
Goummih, S
Tan, Jjit16@pitt.eduJIT16
Alvarez, D
Kass, DJdjk61@pitt.eduDJK61
Rojas, Mmar176@pitt.eduMAR176
de Mattos, TL
Parra, E
Stifano, G
Capelozzi, VL
Simms, RW
Lafyatis, Rlafyatis@pitt.eduLAFYATIS
Date: 1 January 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Arthritis Research and Therapy
Volume: 18
Number: 1
DOI or Unique Handle: 10.1186/s13075-016-1054-6
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
ISSN: 1478-6354
Date Deposited: 25 Jul 2016 13:53
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/28615

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