In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2023 ( 2023-2-11), p. 1-13
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1942-0994
,
1942-0900
DOI:
10.1155/2023/8324504
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2023
detail.hit.zdb_id:
2455981-7
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