Gene expression in bronchial biopsies from subjects with persistent asthma and asthma in remission

EUROPEAN RESPIRATORY JOURNAL(2017)

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摘要
Introduction: No definite cure is available yet for asthma. A subset of asthmatics goes into spontaneous remission and becomes symptom free. Comparison of gene expression in patients with persistent asthma and asthma remission may provide better understanding of the biological mechanisms leading to the remission of asthma and the identification of novel therapeutic targets. Aim: To find differential gene expression in bronchial biopsies from patients with persistent asthma and subjects with well-documented asthma remission. Methods: We performed RNA sequencing in RNA isolated from bronchial biopsies from 25 patients with persistent asthma and 38 subjects with asthma remission, who did not use inhaled corticosteroids. Asthma remission was defined as no symptoms in the last 3 years and no medication in the past 3 months. Differences in raw read counts between persistent asthma and asthma remission were analysed using DESeq2 adjusting for age, gender and smoking status as possible confounders. The FDR was controlled at 10%. Results: We found that the expression of keratin 13 ( KRT13 ) was lower in subjects with complete asthma remission compared to persistent asthmatics (log2FC = 5.4, q-value = 0.078). KRT13 encodes a subunit of keratin intermediate filaments characteristic of squamous epithelium and (bronchial) basal cells. Conclusion: This is the first study on gene expression in bronchial biopsies from asthma remission subjects. We demonstrate that the expression of KRT13 is lower in bronchial biopsies from subjects in remission compared to persistent asthmatics, suggesting less squamous metaplasia and/or basal cell hyperplasia in the airways. Funded by GlaxoSmithKline
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