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Objective: MicroRNAs (miRNAs) 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 SSc-ILD patients. A chronic lung fibrotic murine model was used.
Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by 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 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of 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 showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice.
Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs 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.
Overall design: Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
Accession | PRJNA321200; GEO: GSE81292 |
Data Type | Transcriptome or Gene expression |
Scope | Multiisolate |
Organism | Homo sapiens[Taxonomy ID: 9606] Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens |
Publications | Christmann RB et al., "miR-155 in the progression of lung fibrosis in systemic sclerosis.", Arthritis Res Ther, 2016 Jul 5;18(1):155 |
Grants | - "TSLP profibrotic signaling and its interaction with TGF-beta" (Grant ID K08 AR065507, National Institute of Arthritis and Musculoskeletal and Skin Diseases)
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Submission | Registration date: 10-May-2016 Boston University School of Medicine |
Relevance | Medical |
Project Data:
Resource Name | Number of Links |
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Publications |
PubMed | 1 |
PMC | 1 |
Other datasets |
GEO DataSets | 1 |
GEO Data DetailsParameter | Value |
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Data volume, Spots | 241480 |
Data volume, Processed Mbytes | 3 |
Data volume, Supplementary Mbytes | 45 |