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| Status |
Public on Aug 01, 2016 |
| Title |
Expression of miRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls. |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA 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 |
|
| Submission date |
May 10, 2016 |
| Last update date |
Feb 26, 2021 |
| Contact name |
Romy B Christmann |
| E-mail(s) |
romy.souza@gmail.com
|
| Phone |
6176384309
|
| Organization name |
Boston University School of Medicine
|
| Street address |
715 Albany Street E5
|
| City |
Boston |
| State/province |
MASSACHUSETTS |
| ZIP/Postal code |
02118-2531 |
| Country |
USA |
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| Platforms (1) |
| GPL16384 |
[miRNA-3] Affymetrix Multispecies miRNA-3 Array |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA321199 |
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