Effect of the S۱۰۰A۹/AMPK pathway on PM۲.۵-mediated mouse lung injury

Objective(s): Particulate matter ۲.۵ (PM۲.۵), particles with an aerodynamic diameter less than ۲.۵ µm, affect lung function and increase respiratory disease incidence and mortality rate. The molecular mechanism of lung injury and epithelial damage after PM۲.۵ exposure is not completely clear.Materials and Methods: Mouth-nose exposure of mice was performed with PM۲.۵ or neutral saline. In vitro experiments were conducted to investigate the role of the S۱۰۰A۹/AMPK pathway in PM۲.۵-mediated lung injury.Results: PM۲.۵ exposure in mice caused lung epithelial damage, alveolar wall thickening, and alveolar wall structure destruction. The ۱۶S rRNA sequencing results suggested that the microecology structure of lung tissue was altered after PM۲.۵ exposure. Proteomic sequencing was performed to explore the underlying mechanism, and ۷۱ 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, PM۲.۵ exposure in mice increased the level of S۱۰۰A۹ 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 CD۳۶ and CPT۱, which leads to mitochondrial damage of PM۲.۵-exposed cells and injury or death of lung epithelial cells. siRNA-S۱۰۰A۹ 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 PM۲.۵ exposure.

کلیدواژه ها:

AMPK ATP ، Lung injury ، PM۲.۵ ، ROS ، S۱۰۰A۹