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Updated: Mar 18, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
miR-155 in the progression of lung fibrosis in systemic sclerosis
Romy B Christmann1, Alicia Wooten2, Percival Sampaio-Barros3
1Boston University School of Medicine, E501, Arthritis Center, Medical Campus, 72 East Concord Street, Boston, MA, 02118-2526, USA. romy.souza@gmail.com.
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.
Insights
MicroRNAs (miRNAs) are dysregulated in systemic sclerosis associated interstitial lung disease (SSc-ILD). Targeting miR-155 may offer a new therapeutic approach for SSc-ILD progression.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRNAs) regulate mRNA stability and are implicated in gene expression changes in systemic sclerosis associated interstitial lung disease (SSc-ILD).
- Investigating miRNA expression in SSc-ILD lung tissue and cells is crucial for understanding disease pathogenesis.
- A chronic lung fibrotic murine model was utilized to study miRNA roles in fibrosis.
Purpose of the Study:
- To analyze miRNA gene expression in patients with SSc-ILD.
- To identify specific miRNAs associated with disease progression and lung function.
- To explore the therapeutic potential of targeting miRNAs, particularly miR-155, in SSc-ILD.
Main Methods:
- RNA isolation from lung tissue of SSc-ILD patients and controls.
- Microarray, quantitative PCR, and Nanostring analysis of miRNA and mRNA.
- Pathway analysis using DIANA-miRPath v2.0 and a bleomycin-induced lung fibrosis mouse model.
Main Results:
- 185 differentially expressed miRNAs were identified between SSc-ILD patients and controls.
- miR-155 and miR-143 correlated with high-resolution computed tomography (HRCT) score progression.
- miR-155 deficiency in mice resulted in milder lung fibrosis and improved survival.
Conclusions:
- miRNAs are dysregulated in the lungs and peripheral blood mononuclear cells (PBMC) of SSc-ILD patients.
- miRNA dysregulation, particularly miR-155, plays a role in SSc-ILD progression.
- Targeting miR-155 presents a potential novel therapeutic strategy for SSc-ILD.
