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
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.
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Article
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Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Christmann, RB | | | | Wooten, A | | | | Sampaio-Barros, P | | | | Borges, CL | | | | Carlos, CR | | | | Kairalla, RA | | | | Feghali-Bostwick, C | | | | Ziemek, J | | | | Mei, Y | | | | Goummih, S | | | | Tan, J | jit16@pitt.edu | JIT16 | | Alvarez, D | | | | Kass, DJ | djk61@pitt.edu | DJK61 | | Rojas, M | mar176@pitt.edu | MAR176 | | de Mattos, TL | | | | Parra, E | | | | Stifano, G | | | | Capelozzi, VL | | | | Simms, RW | | | | Lafyatis, R | lafyatis@pitt.edu | LAFYATIS | |
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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: |
30 Mar 2021 10:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/28615 |
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