Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury
Objective(s): 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.Materia...
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Mashhad University of Medical Sciences
2025-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25029_6b3a3049a9c1a15b14dd7241dcd61bdd.pdf |
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| author | Yunxia Li Yunxin Bai Shiyu Tang Ye Sun Zhe Wang Biao Yang Guangyan Liu |
| author_facet | Yunxia Li Yunxin Bai Shiyu Tang Ye Sun Zhe Wang Biao Yang Guangyan Liu |
| author_sort | Yunxia Li |
| collection | DOAJ |
| description | Objective(s): 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. |
| format | Article |
| id | doaj-art-05bc520ab9ed438087031c8daca4c3cc |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-05bc520ab9ed438087031c8daca4c3cc2025-08-20T03:56:45ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-01-0128112112910.22038/ijbms.2024.80242.1737425029Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injuryYunxia Li0Yunxin Bai1Shiyu Tang2Ye Sun3Zhe Wang4Biao Yang5Guangyan Liu6Department of Respiratory and Critical Care Medicine, The Fourth People’s Hospital of Shenyang, Shenyang 110000, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang. No. 146, Huanghe North Street, Shenyang, People’s Republic of ChinaDepartment of Pathophysiology, Shenyang Medical College, Shenyang. No. 146, Huanghe North Street, Shenyang, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang. No. 146, Huanghe North Street, Shenyang, People’s Republic of ChinaDepartment of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang. No. 146, Huanghe North Street, Shenyang, People’s Republic of ChinaGraduate school, Shenyang Medical College, Shenyang. No. 146, Huanghe North Street, Shenyang, People’s Republic of ChinaObjective(s): 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.https://ijbms.mums.ac.ir/article_25029_6b3a3049a9c1a15b14dd7241dcd61bdd.pdfampk atplung injurypm2.5ross100a9 |
| spellingShingle | Yunxia Li Yunxin Bai Shiyu Tang Ye Sun Zhe Wang Biao Yang Guangyan Liu Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury Iranian Journal of Basic Medical Sciences ampk atp lung injury pm2.5 ros s100a9 |
| title | Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury |
| title_full | Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury |
| title_fullStr | Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury |
| title_full_unstemmed | Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury |
| title_short | Effect of the S100A9/AMPK pathway on PM2.5-mediated mouse lung injury |
| title_sort | effect of the s100a9 ampk pathway on pm2 5 mediated mouse lung injury |
| topic | ampk atp lung injury pm2.5 ros s100a9 |
| url | https://ijbms.mums.ac.ir/article_25029_6b3a3049a9c1a15b14dd7241dcd61bdd.pdf |
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