The Wnt/β-catenin pathway regulates inflammation and apoptosis in ventilator-induced lung injury

Ventilator-induced lung injury (VILI) may be caused by incorrect mechanical ventilation (MV), and its progression is mainly related to inflammatory reaction, Apoptosis and oxidative stress. The Wnt/β-catenin pathway can modulate inflammation and Apoptosis, however, its role in VILI is unknown. This research aims to explore the role of the Wnt/β-catenin pathway in VILI. VILI models were established using rats and type II alveolar epithelial cells. GSK-3β, β-catenin and cyclin D1 were determined using western blot and immunofluorescence. Apoptosis of lung tissues was evaluated using TUNEL, flow cytometry, Bax and Bcl2 protein. IL-1β, IL-6 and TNF-α were detected via ELISA. Lung pathological injury was evaluated through hematoxylin and eosin staining. Lung permeability was evaluated by the ratio of dry to wet weight of lung tissue and the total protein level of bronchoalveolar lavage fluid. The results showed that GSK-3β expression was enhanced and β-catenin expression was diminished in lung tissue under MV. SB216763 increased β-catenin and cyclin D1 expression by inhibiting GSK-3β expression and inhibited the inflammatory response and Apoptosis of lung, alleviated pulmonary edema and lung tissue permeability, and significantly mitigated lung injury. However, inhibition of β-catenin expression by MSAB attenuated the anti-inflammatory and anti-apoptotic effects of SB216763 in VILI. Overall, this study demonstrates that the Wnt/β-catenin pathway activation in MV may play an anti-inflammatory and anti-apoptotic role, thereby alleviating lung injury and delaying VILI progression, which may be a key point of intervention in VILI.

GSK-3β; SB216763; Wnt/β-catenin pathway; mechanical ventilation; ventilator-induced lung injury.