Affiliation:
1. Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
2. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
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.
Funder
Guangdong Basic and Applied Basic Research Foundation
Subject
Cell Biology,Aging,General Medicine,Biochemistry
Cited by
1 articles.
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