Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model
Abstract
1. Introduction
2. Results
2.1. Suppression of Endotoxin-Enhanced MV-Induced Microvascular Leak, Lung Edema, Hypoxemia, ER Accumulation, Oxidative Stress, IL-6, and MMP-9 Production, and ER Stress Protein Expression Through 4-PBA
2.2. Endotoxin-Augmented MV-Induced PI3K-γ Protein Expression
2.3. Reduction In Endotoxin-Augmented MV-Induced Lung Inflammation and ER Stress in PI3K-γ-Deficient Mice
2.4. Inhibition of MV-Induced Effects on Endotoxin-Enhanced CHOP Expression, Caspase-3, and Epithelial Apoptosis in PI3K-γ-Deficient Mice
3. Discussion
4. Materials and Methods
4.1. Experimental Animals
4.2. Pharmacological Inhibitors
4.3. Measurement of Inflammatory Cytokines
4.4. Immunoblot Analysis of ER Stress and PI3K-γ
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALI | Acute lung injury |
MV | Mechanical ventilation |
VILI | Ventilator-induced lung injury |
ER stress | Endoplasmic reticulum stress |
GRP78 | 78 kDa glucose-regulated protein |
PERK | Protein kinase RNA-like ER kinase |
IRE1a | Inositol-requiring enzyme 1a |
ATF6 | Activating transcription factor 6 |
PI3K-g | Phosphoinositide 3-kinase-g |
LPSs | Lipopolysaccharides |
IL-6 | Interleukin-6 |
MMP-9 | Metalloproteinase-9 |
UPR | Unfolded protein response |
XBP-1 | X-box binding protein |
CHOP | CCAAT/enhancer-binding protein homologous protein |
MDA | Malondialdehyde |
SOD | Sodium dismutase |
EBD | Evans blue dye |
TEM | Transmission electron microscopy |
TUNEL t | Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. |
4-PBA | 4-phenylbutyric acid |
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Li, L.-F.; Yu, C.-C.; Huang, C.-Y.; Wu, H.-P.; Chu, C.-M.; Liu, P.-C.; Liu, Y.-Y. Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model. Int. J. Mol. Sci. 2025, 26, 5761. https://doi.org/10.3390/ijms26125761
Li L-F, Yu C-C, Huang C-Y, Wu H-P, Chu C-M, Liu P-C, Liu Y-Y. Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model. International Journal of Molecular Sciences. 2025; 26(12):5761. https://doi.org/10.3390/ijms26125761
Chicago/Turabian StyleLi, Li-Fu, Chung-Chieh Yu, Chih-Yu Huang, Huang-Pin Wu, Chien-Ming Chu, Ping-Chi Liu, and Yung-Yang Liu. 2025. "Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model" International Journal of Molecular Sciences 26, no. 12: 5761. https://doi.org/10.3390/ijms26125761
APA StyleLi, L.-F., Yu, C.-C., Huang, C.-Y., Wu, H.-P., Chu, C.-M., Liu, P.-C., & Liu, Y.-Y. (2025). Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model. International Journal of Molecular Sciences, 26(12), 5761. https://doi.org/10.3390/ijms26125761