Cigarette Smoke-Induced Acquired Dysfunction of Cystic Fibrosis Transmembrane Conductance Regulator in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Figure 3

The cystic fibrosis transmembrane conductance regulator (CFTR) is a potential target for COPD treatment. The proper CFTR function is critical in maintaining the homeostasis of airway surface hydration and mucociliary clearance of normal airway epithelia. Cigarette smoke is able to induce excessive mucus secretion and has a negative impact on CFTR activation. The consequences of genetic and acquired CFTR dysfunction in patients with CB and COPD lead to a disreputable homeostasis of mucus and decreased ASL volume. The dehydrated mucus impairs the mucus clearance. Therefore, strategies that restore the CFTR function at different levels (mRNA and protein expression, stability, CFTR gating, and trafficking) using CFTR modulators (potentiator/corrector) and cAMP agonist (PDE inhibitors) may provide novel therapeutic approaches in obstructive pulmonary diseases, such as CB of COPD. The image on the left panel shows the cigarette smoke-induced CFTR dysfunction at different levels, and that in right the panel shows potential therapeutic interventions to restore CFTR function in cigarette smoke-exposed CFTR dysfunction. The red blocked line indicates an inhibition, and the green line with arrow represents an induction.