Overexpression of FoxM1 Enhanced the Protective Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Lipopolysaccharide-Induced Acute Lung Injury through the Activation of Wnt/ β -Catenin Signaling.

Background: Mesenchymal stem cell- (MSC-) based cell and gene therapies have made remarkable progress in alleviating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the benefits of Forkhead box protein M1 ( FoxM1 ) gene-modified MSCs in the treatment of ALI have not been studied.
Methods: We evaluated the therapeutic effects of FoxM1 -modified MSCs in ALI mice induced by lipopolysaccharide (LPS) by quantifying the survival rate, lung weight ratio (wet/dry), and contents of bronchoalveolar lavage fluid. In addition, microcomputed tomography, histopathology, Evans Blue assay, and quantification of apoptosis were performed. We also explored the underlying mechanism by assessing Wnt/ β -catenin signaling following the treatment of mice with FoxM1 -modified MSCs utilizing the Wnt/ β -catenin inhibitor XAV-939.
Results: Compared with unmodified MSCs, transplantation of FoxM1 -modified MSCs improved survival and vascular permeability; reduced total cell counts, leukocyte counts, total protein concentrations, and inflammatory cytokines in BALF; attenuated lung pathological impairments and fibrosis; and inhibited apoptosis in LPS-induced ALI/ARDS mice. Furthermore, FoxM1 -modified MSCs maintained vascular integrity during ALI/ARDS by upregulating Wnt/ β -catenin signaling, which was partly reversed via a pathway inhibitor.
Conclusion: Overexpression of FoxM1 optimizes the treatment action of MSCs on ALI/ARDS by inhibiting inflammation and apoptosis and restoring vascular integrity partially through Wnt/ β -catenin signaling pathway stimulation.
Competing Interests: The researchers have not disclosed any conflicts of interest.
(Copyright © 2023 Yuling Luo et al.)