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.

BackgroundDeoxythymidylate kinase (DTYMK) is a rate-limiting enzyme in pyrimidine metabolism. Crucially, it is overexpressed in a variety of tumors and is associated with poor prognosis in liver cancer. The role of DTYMK in lung adenocarcinoma remains poorly understood, particularly with respect to immune infiltration. MethodsThe present study aimed to compare the expression of DTYMK between normal tissues, lung adenocarcinoma, and other cancer types using data obtained via The Cancer Genome Atlas, Tumor Immune Estimation Resource 2.0, Gene Expression Database of Normal and Tumor Tissues 2, and Gene Expression Profiling Interactive Analysis (GEPIA). The prognostic value of DTYMK in patients with lung adenocarcinoma was evaluated using GEPIA and Kaplan–Meier plotter. STRING and GeneMANIA were employed to assess protein and gene interaction with DTYMK. R software and TISIDB were used to analyze the correlation between DTYMK expression and immune infiltration. Finally, we validated DTYMK protein expression in lung adenocarcinoma using the UALCAN and HPA databases. ResultsDTYMK expression was significantly increased in various cancer and lung adenocarcinoma tissues (p < 0.05), and was associated with poor prognosis (p < 0.05) in patients with lung adenocarcinoma. In addition, DTYMK was negatively associated with the vast majority of immune cells in lung adenocarcinoma.ConclusionsIncreased expression of DTYMK is associated with poor prognosis in lung adenocarcinoma patients. DTYMK may serve as a potential prognostic biomarker in lung adenocarcinoma. In addition, DTYMK may influence the progression and prognosis of lung adenocarcinoma by influencing the immune microenvironment of tumors.