J Biol Regul Homeost Agents. 2020 May-Jun;34(3):953-960. doi: 10.23812/20-50-A-54.


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Effects of fine particulate PM2.5 on emphysema of mice via regulating FOXO3A/BIM axis.

Wang WL1, Zhao YJ1.

Author information

1 Department of Respiratory Medicine, The Third hospital of JiLin University, Changchun, China.


This study aims to investigate the role of PM2.5 exposure in inducing apoptosis of alveolar epithelial cells and thereafter emphysema in mice, and the underlying mechanism. PM2.5 exposure model in mice was constructed. Lung tissues were harvested from healthy mice and model mice for hematoxylin and eosin (H&E) staining. Protein levels of Forkhead box O3 (FOXO3A) and BIM in lung tissues were detected by Western blot. Subsequently, A549 cells were induced with increased doses of PM2.5, followed by determination of relative levels of FOXO3A, BIM (Bcl-2 interacting mediator of cell death) and clv-caspase3. Apoptosis in PM2.5-exposed A549 cells was assessed. Chromatin immunoprecipitation (ChIP) assay was conducted to uncover the interaction between FOXO3A and BIM. Finally, regulatory effects of FOXO3A/BIM on apoptosis of A549 cells were determined. PM2.5 exposure resulted in expansion of alveolar spatial structure and decline of lung function, thus leading to emphysema in mice. Protein levels of FOXO3A and BIM were markedly upregulated in lungs of model mice. Relative levels of FOXO3A, BIM and clv-caspase3 were enhanced in PM2.5 -exposed A549 cells, which were reversed by transfection of si-FOXO3A. ChIP assay confirmed that FOXO3A was able to regulate BIM transcription through binding its promoter regions. Importantly, regulatory effects of FOXO3A on apoptosis of PM2.5 -exposed A549 cells were partially reversed by overexpression of BIM. PM2.5 exposure leads to upregulation of FOXO3A, which triggers BIM transcription, thus inducing apoptosis of alveolar epithelial cells and emphysema in mice.


BIM, FOXO3A, PM2.5, alveolar epithelial cells, apoptosis, emphysema

Publication type

  • Journal Article

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