Stress stimulation promotes the injury repair process of airway epithelial cells through the [Cl−]i−FAK signaling axis

The airway epithelium serves as a critical interface with the external environment, making it vulnerable to various external stimuli. Airway epithelial stress acts as a catalyst for the onset of numerous pulmonary and systemic diseases. Our previous studies have highlighted the impact of acute stress stimuli, especially bacterial lipopolysaccharide (LPS) and hydrogen peroxide (H₂O₂), on the continuous elevation of intracellular chloride concentration ([Cl⁻]_i). However, the precise mechanism behind this [Cl−]_i elevation and the consequential effects of such stress on the injury repair function of airway epithelial cells remain unclear. Our findings indicate that H₂O₂ induces an elevation in [Cl⁻]_i by modulating the expression of CF transmembrane conductance regulator (CFTR) and Ca-activated transmembrane protein 16 A (TMEM16A) in airway epithelial cells (BEAS-2B), whereas LPS achieves this solely through CFTR. Subsequently, the elevated [Cl⁻]_i level facilitated the injury repair process of airway epithelial cells by activating focal adhesion kinase (FAK). In summary, the [Cl⁻]_i−FAK axis appears to play a promoting effect on the injury repair process triggered by stress stimulation. Furthermore, our findings suggest that abnormalities in the [Cl⁻]_i−FAK signaling axis may play a crucial role in the pathogenesis of chronic airway diseases. Therefore, controlling the structure and function of airway epithelial barriers through the modulation of [Cl⁻]_i holds promising prospects for future applications in managing and treating such conditions.