Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model
Abstract
:1. Introduction
2. Results
2.1. GSK-3 Inhibition by CHIR99021 Attenuates Lung Injury in LPS-Induced ALI
2.2. GSK-3 Inhibition by CHIR99021 Does Not Affect the Recruitment of Inflammatory Cells and the Production of Pro- and Anti-Inflammatory Cytokines in LPS-Induced ALI
2.3. GSK-3 Inhibition by CHIR99021 Promotes the Proliferation of Cells Expressing AECI and AECII Markers in LPS-Induced ALI
2.4. GSK-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Population Renewal in LPS-Induced ALI
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Experimental Design
4.3. LPS-Induced ALI Mouse Model
4.4. Histological Examination
4.5. Immunofluorescence
4.6. Bronchoalveolar Lavage Fluid Collection
4.7. Flow Cytometry
4.8. ELISA
4.9. Western Blotting
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Score |
---|---|
Alveoli congestion | 0: Minimal damage; 1: Mild damage 2: Moderate damage; 3: Severe damage; 4: Maximal damage |
Immune infiltration | 0: Minimal damage; 1: Mild damage 2: Moderate damage; 3: Severe damage; 4: Maximal damage |
Number of macrophages | 0: <5; 1: 5–10; 2: 10–20; 3: 20–50; 4: >50 |
Number of neutrophils | 0: <5; 1: 5–10; 2: 10–20; 3: 20–50; 4: >50 |
Hyaline membranes | 0: Minimal damage; 1: Mild damage 2: Moderate damage; 3: Severe damage; 4: Maximal damage |
Alveolar wall thickness | 0: equal to control; 1: 2x; 2: 2x–4x; 3: >4x |
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Fernandes, R.; Barbosa-Matos, C.; Borges-Pereira, C.; Carvalho, A.L.R.T.d.; Costa, S. Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model. Int. J. Mol. Sci. 2024, 25, 1279. https://doi.org/10.3390/ijms25021279
Fernandes R, Barbosa-Matos C, Borges-Pereira C, Carvalho ALRTd, Costa S. Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model. International Journal of Molecular Sciences. 2024; 25(2):1279. https://doi.org/10.3390/ijms25021279
Chicago/Turabian StyleFernandes, Raquel, Catarina Barbosa-Matos, Caroline Borges-Pereira, Ana Luísa Rodrigues Toste de Carvalho, and Sandra Costa. 2024. "Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model" International Journal of Molecular Sciences 25, no. 2: 1279. https://doi.org/10.3390/ijms25021279