Dataset Information

MiR-155 in the progression of lung fibrosis in systemic sclerosis.

ABSTRACT: 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.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.Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q?

SUBMITTER: Christmann RB

PROVIDER: S-EPMC4932708 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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miR-155 in the progression of lung fibrosis in systemic sclerosis.

Christmann Romy B RB Wooten Alicia A Sampaio-Barros Percival P Borges Claudia L CL Carvalho Carlos R R CR Kairalla Ronaldo A RA Feghali-Bostwick Carol C Ziemek Jessica J Mei Yu Y Goummih Salma S Tan Jiangning J Alvarez Diana D Kass Daniel J DJ Rojas Mauricio M de Mattos Thiago Lemos TL Parra Edwin E Stifano Giuseppina G Capelozzi Vera L VL Simms Robert W RW Lafyatis Robert R

Arthritis research & therapy 20160705 1

<h4>Background</h4>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.<h4>Methods</h4>RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed ...[more]

PMID: 27377409

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Project description:Systemic sclerosis is a rare connective tissue disease; and interstitial lung disease (SSc-ILD) is associated with significant morbidity and mortality. There are no clinical, radiologic features, nor biomarkers that identify the specific time when patients are at risk for progression at which the benefits from treatment outweigh the risks. Our study aimed to identify blood protein biomarkers associated with progression of interstitial lung disease in patients with SSc-ILD using an unbiased, high-throughput approach. We classified SSc-ILD as progressive or stable based on change in forced vital capacity over 12 months or less. We profiled serum proteins by quantitative mass spectrometry and analyzed the association between protein levels and progression of SSc-ILD via logistic regression. The proteins associated with at a p value of < 0.1 were queried in the ingenuity pathway analysis (IPA) software to identify interaction networks, signaling, and metabolic pathways. Through principal component analysis, the relationship between the top 10 principal components and progression was evaluated. Unsupervised hierarchical clustering with heatmapping was done to define unique groups. The cohort consisted of 72 patients, 32 with progressive SSc-ILD and 40 with stable disease with similar baseline characteristics. Of a total of 794 proteins, 29 were associated with disease progression. After adjusting for multiple testing, these associations did not remain significant. IPA identified five upstream regulators that targeted proteins associated with progression, as well as a canonical pathway with a higher signal in the progression group. Principal component analysis showed that the ten components with the highest Eigenvalues represented 41% of the variability of the sample. Unsupervised clustering analysis revealed no significant heterogeneity between the subjects. We identified 29 proteins associated with progressive SSc-ILD. While these associations did not remain significant after accounting for multiple testing, some of these proteins are part of pathways relevant to autoimmunity and fibrogenesis. Limitations included a small sample size and a proportion of immunosuppressant use in the cohort, which could have altered the expression of inflammatory and immunologic proteins. Future directions include a targeted evaluation of these proteins in another SSc-ILD cohort or application of this study design to a treatment naïve population.

Dataset Information

MiR-155 in the progression of lung fibrosis in systemic sclerosis.

Publications

miR-155 in the progression of lung fibrosis in systemic sclerosis.

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