Abstract
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.
Highlights
Mechanical ventilation induces lung injury by damaging alveolar epithelial cells (AECs), but the pathogenesis remains unknown
We found that Ventilator-induced lung injury (VILI) can decrease Focal adhesion kinase (FAK) expression significantly in vitro and vivo, whereas supplementation with FAK attenuates injury induced by high-volume mechanical ventilation (HMV) via the Akt pathway
We evaluated the FAK expression level in AECs by IHC, and the results showed that High-volume mechanical ventilation (HMV) treatment, compared to control, clearly decreased FAK expression levels, which is consistent with some other studies[6,7]
Summary
Mechanical ventilation induces lung injury by damaging alveolar epithelial cells (AECs), but the pathogenesis remains unknown. 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 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. Previous studies have revealed that FAK plays an important role in the regulation of AECs. Unfried K et al suggested that carbon nanoparticles can contribute to the proliferation of lung epithelial cells through the FAK-PI3K-Akt pathway[4]. We created a VILI mouse model and investigated FAK expression in AECs. We found that VILI can decrease FAK expression significantly in vitro and vivo, whereas supplementation with FAK attenuates injury induced by high-volume mechanical ventilation (HMV) via the Akt pathway. We found that FAK can promote AEC proliferation and adhesion and prevent cells from undergoing apoptosis, which promotes the regeneration of AECs after injury
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