Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
Youfeng Zhu1, Yang Chen1, Di Xie2
1Department of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China.
Background:
AKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.
Methods:
The mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.
Results:
AKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.
Conclusion:
Collectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.
Insights
AKT3 modulates macrophage function to protect against lung injury in ventilator-associated pneumonia (VAP). Macrophage depletion attenuates ferroptosis by regulating the AKT3/GPX4 pathway, mitigating VAP-induced lung damage.
Area of Science:
- Molecular biology
- Immunology
- Oncology
Background:
- AKT3's role in lung cancer is known, but its function in ventilator-associated pneumonia (VAP) remains unclear.
- This study investigates AKT3's involvement in macrophages during VAP.
Purpose of the Study:
- To elucidate the role of AKT3 in macrophages during ventilator-associated pneumonia.
- To explore the therapeutic potential of targeting AKT3 in VAP.
Main Methods:
- Analysis of AKT3 mRNA levels using TCGA and GEO datasets.
- In vivo experiments to investigate AKT3's role in VAP.
- Macrophage depletion experiments to assess effects on lung epithelial cells and ferroptosis markers.
Main Results:
- AKT3 exhibits differential expression in normal and tumor tissues, with immunomodulatory and inflammatory roles in lung cancer.
- Macrophage depletion protected lung epithelial cells, altering expression of MMP9, MMP19, FTH, FTL, and GPX4.
- Macrophage depletion attenuated ferroptosis in lung epithelial cells by modulating AKT3 during VAP.
Conclusions:
- Further validation of AKT3's immunoregulatory function in lung cancer is warranted.
- Macrophage depletion mitigates lung injury in VAP by modulating the AKT3/GPX4 pathway.
