Enhancement of FAK alleviates ventilator-induced alveolar epithelial cell injury.

Mechanical ventilation induces lung injury by damaging alveolar epithelial cells (AECs), but the pathogenesis remains unknown. Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is involved in cell growth and intracellular signal transduction pathways. This study explored the potential role of FAK in AECs during lung injury induced by mechanical ventilation. High-volume mechanical ventilation (HMV) was used to create a mouse lung injury model, which was validated by analysis of lung weight, bronchoalveolar lavage fluid and histological investigation. The expression of FAK and Akt in AECs were evaluated. In addition, recombinant FAK was administered to mice via the tail vein, and then the extent of lung injury was assessed. Mouse AECs were cultured in vitro, and FAK expression in cells under stretch was investigated. The effects of FAK on cell proliferation, migration and apoptosis were investigated. The results showed that HMV decreased FAK expression in AECs of mice, while FAK supplementation attenuated lung injury, reduced protein levels/cell counts in the bronchoalveolar lavage fluid and decreased histological lung injury and oedema. The protective effect of FAK promoted AEC proliferation and migration and prevented cells from undergoing apoptosis, which restored the integrity of the alveoli through Akt pathway. Therefore, the decrease in FAK expression by HMV is essential for injury to epithelial cells and the disruption of alveolar integrity. FAK supplementation can reduce AEC injury associated with HMV.