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Status |
Public on Aug 01, 2016 |
Title |
Expression of mRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls (HC) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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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.
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Contributor(s) |
Christmann R, Sampaio-Barros P |
Citation(s) |
27377409 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
K08 AR065507 |
TSLP profibrotic signaling and its interaction with TGF-beta |
BOSTON UNIVERSITY |
Romy Beatriz Christmann |
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Submission date |
May 10, 2016 |
Last update date |
Oct 31, 2016 |
Contact name |
Romy B Christmann |
E-mail(s) |
romy.souza@gmail.com
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Phone |
6176384309
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Organization name |
Boston University School of Medicine
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Street address |
715 Albany Street E5
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City |
Boston |
State/province |
MASSACHUSETTS |
ZIP/Postal code |
02118-2531 |
Country |
USA |
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Platforms (1) |
GPL18991 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array [HGU133A2_Hs_ENTREZG_16.0.0] |
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Samples (20)
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This SubSeries is part of SuperSeries: |
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Relations |
BioProject |
PRJNA321200 |