Bronchial airway expression of mucin-related, ENaC and chloride channel genes in COPD and non-COPD smokers compared to former and never smokers

Abstract

Rationale: Smoking is a major risk factor for perturbing the airway mucosal barrier and developing chronic obstructive pulmonary disease (COPD). However, our understanding of its influence on mucin production and airway surface hydration is incomplete.

Aim: We aimed to assess how mucin-related, epithelial sodium channels (ENaC) and chloride channel gene expression in bronchial biopsies are altered by current smoking exposure in COPD and non-COPD participants.

Methods: RNA-seq expression was assessed in bronchial biopsies from three cohorts including a COPD cohort (38 smokers; 18 former smokers), a non-COPD cohort (40 never-smokers and 37 smokers) and a Stop-smoking cohort (11 COPD smokers, 5 non-COPD smokers, before and after 1-year smoking cessation). Expression levels of 23 genes were investigated, including mucin-related, ENaC (SCNN1A, SCNN1B, SCNN1D, SCNN1G) and chloride channel genes (CFTR, ANO1), using edgeR. Differences at a Benjamini–Hochberg corrected P-value < 0.05 were considered significant.

Results: Expression levels of bronchial epithelial mucin and ENaC genes, but not chloride channel genes were altered by smoking status in COPD patients and non-COPD controls. MUC5AC, MUC1, MUC16, MUC2, SCNN1A were increased in COPD and non-COPD smokers, whereas SCNN1G expression was decreased. Their expression levels were found to be reversible after 1-year smoking cessation.

Conclusions: The altered expression levels of mucin and ENaC genes by current smoking suggest that these may contribute to increased mucus production and disturbed airway surface hydration, which harbor a reversible potential after smoking cessation.