Micro-RNA involvement in Progressive interstitial lung disease associated to systemic sclerosis

International Conference and Exhibition on Lung Disorders & Therapeutics

July 13-15, 2015 Baltimore, Maryland, USA

Romy Beatriz Christmann

Posters-Accepted Abstracts: J Pulm Respir Med

Abstract :

Objective: Systemic sclerosis associated interstitial lung disease (SSc-ILD) is still one of the leading causes of mortality in SSc patients. We analyzed the micro-RNA (miRNA) gene expression of lung tissue and serum in prospective cohorts of patients with SSc-ILD and compared to controls. Methods: RNA was isolated from lung tissue obtained by open lung biopsy in 12 SSc-ILD patients and from 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. miRNA and mRNA were analyzed by microarray and the resulting data analyzed by MirConnX network software. miRNA expression was correlated with mRNA expression and changes in the HRCT score (FibMax). Quantitative polymerase chain reaction (qPCR) was performed to confirm differential levels of miRNA. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (p<0.05, q<0.25). The MirConnX analysis in the lungs revealed 4 relevant upregulated miRNA in the complex mRNA-miRNA network: mir-182, mir-141, mir-155, and mir-195. Mir-21 was also found highly expressed in SSc-ILD lungs. mir-155 and mir-21 correlated strongly with altered lung mRNA expression such as CXCL13, SPP1, collagens and others. Several miRNAs were confirmed to be upregulated in the lungs of SSc-ILD by qPCR. Most importantly, both mir-155 and mir- 21 correlated strongly with an image score of lung fibrosis (delta FibMax) with higher expression related to worsening disease. Conclusions: miRNAs are dysregulated in lungs of SSc-ILD patients with mir-155 and mir-21 associated with progressive lung fibrosis. miRNAs show great potential as biomarkers for progressive SSc-ILD.