Abnormal DNA methylation patterns distinguish airway smooth muscle cell function in asthma and asthma severity http://ow.ly/cTrK30iCwVK
To the Editor:
Asthma is a chronic airway inflammatory disorder characterised by airway hyperresponsiveness, inflammation and remodelling, including airway smooth muscle cell (ASMC) hyperplasia and subepithelial airway fibrosis [1, 2]. ASMCs from severe asthmatics are hyperproliferative, release more pro-inflammatory cytokines and are corticosteroid-insensitive compared with those from healthy individuals and non-severe asthma patients [3, 4]. Genetic and epigenetic processes such as miRNA expression and DNA methylation have been implicated in asthma pathogenesis . Indeed, DNA methylation is altered in asthmatic blood cells  and may be a biomarker of atopy .
We hypothesised that genome-wide analysis of DNA methylation associated with altered mRNA and miRNA expression would reveal insights into pathways driving severe asthma particularly in ASMCs whose function is abnormal in disease. We analysed the interconnections and functional relevance of differences in DNA methylation status and the expression of mRNAs and miRNAs in ASMCs cultured from bronchial biopsies obtained from five healthy subjects, five non-severe asthma patients (NSA) and five severe asthma patients (SA), at baseline and following stimulation with 2.5% fetal calf serum (FCS) and transforming growth factor (TGF)-β (1 ng·mL−1) [3, 4]. This stimulus is known to induce ASMC proliferation and enhance the release of inflammatory mediators in a severity dependent manner [3, 4]. SA and NSA were defined as previously described [1, 2]. Healthy subjects had no previous history of asthma and provocative concentration causing a 20% fall in forced expiratory volume in 1 s >16 mg·mL−1. Full patient demographics are shown in table 1. The study was approved by the Ethics Committee of the Royal Brompton and Harefield Hospital NHS Trust and all subjects gave written informed consent.