Cigarette smoke extract induces activation of β-catenin/TCF signaling through inhibiting GSK3β in human alveolar epithelial cell line

Cigarette smoke is known to have various injurious and cytotoxic effects on alveolar epithelial cells. However, the mechanism about the effects caused by cigarette smoke on alveolar epithelial cells remains unclear.In the present study, we first validated that cigarette smoke extract (CSE) impaired the viability of alveolar epithelial cells (A549 cells) and resulted in some morphological changes. Next, we found that glycogen synthase kinase 3β (GSK3β) was highly expressed in A549 cells, and CSE significantly inhibited GSK3β by reducing GSK3β expression and increasing inactive phosphorylated GSK3β. It was also observed that CSE promoted β-catenin accumulation and nuclear translocation, and further activated β-catenin/TCF signaling. Finally, we demonstrated that GSK3β over-expression promoted the degradation of β-catenin and abolished β-catenin/TCF transcriptional activity that was induced by CSE in alveolar epithelial cells. These results suggest that CSE induces the activation of β-catenin/TCF signaling through inhibiting GSK3β, implying a possible mechanism responsible for the injurious and cytotoxic effects on alveolar epithelial cell caused by cigarette smoke.