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Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury
Yunxia Li1, Yuxin Bai2, Shiyu Tang3
1Department of Respiratory and Critical Care Medicine, The Fourth People's Hospital of Shenyang, Shenyang 110000, China.
Objectives:
Particulate matter 2.5 (PM2.5), particles with an aerodynamic diameter less than 2.5 µm, affect lung function and increase respiratory disease incidence and mortality rate. The molecular mechanism of lung injury and epithelial damage after PM2.5 exposure is not completely clear.
Materials And Methods:
Mouth-nose exposure of mice was performed with PM2.5 or neutral saline. In vitro experiments were conducted to investigate the role of the S100A9/AMPK pathway in PM2.5-mediated lung injury.
Results:
PM2.5 exposure in mice caused lung epithelial damage, alveolar wall thickening, and alveolar wall structure destruction. The 16S rRNA sequencing results suggested that the microecology structure of lung tissue was altered after PM2.5 exposure. Proteomic sequencing was performed to explore the underlying mechanism, and 71 differentially expressed proteins were identified. KEGG database analysis of the up-regulated differential proteins revealed regulatory networks, including fat digestion and absorption, the AMPK signaling pathway, and the PPAR signaling pathway. Moreover, PM2.5 exposure in mice increased the level of S100A9 and ROS, leading to reduction of the ATP level. To achieve a sufficient energy supply by increasing fatty acid transfer and oxidation, activated AMPK up-regulates CD36 and CPT1, which leads to mitochondrial damage of PM2.5-exposed cells and injury or death of lung epithelial cells. siRNA-S100A9 and AMPK inhibitors significantly reduced the occurrence of cell damage.
Conclusion:
These results may help to clarify biomarkers and specific mechanisms of lung tissue injury induced by PM2.5 exposure.
Insights
Exposure to fine particulate matter (PM2.5) damages lung epithelial cells by disrupting the S100A9/AMPK pathway. Targeting this pathway may offer new strategies for treating PM2.5-induced lung injury.
Area of Science:
- Environmental Health
- Toxicology
- Molecular Biology
Background:
- Particulate matter 2.5 (PM2.5) exposure is linked to increased respiratory disease and mortality.
- The precise molecular mechanisms underlying PM2.5-induced lung injury remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of lung injury caused by PM2.5 exposure.
- To investigate the role of the S100A9/AMPK pathway in PM2.5-mediated lung damage.
Main Methods:
- Mice were exposed to PM2.5 via inhalation.
- In vitro cell models were used to study the S100A9/AMPK pathway.
- Proteomic and 16S rRNA sequencing were employed to analyze molecular and microecological changes.
Main Results:
- PM2.5 exposure induced lung epithelial damage, alveolar wall thickening, and altered lung microecology.
- Proteomic analysis identified 71 differentially expressed proteins, highlighting the AMPK signaling pathway.
- PM2.5 increased S100A9 and ROS, reducing ATP levels and activating AMPK, leading to mitochondrial damage and cell death. siRNA-S100A9 and AMPK inhibitors mitigated these effects.
Conclusions:
- The S100A9/AMPK pathway is critically involved in PM2.5-induced lung injury.
- These findings may help identify biomarkers and clarify mechanisms for PM2.5 lung tissue damage.
