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 (H2 O2 ), 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 H2 O2 induces an elevation in [Cl- ]i by modulating the expression of CF transmembrane conductance regulator (CFTR) and Ca-activated transmembrane protein 16A (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.