Toxic effects of nanoplastics with different sizes and surface charges on epithelial-to-mesenchymal transition in A549 cells and the potential toxicological mechanism

文献类型： 外文期刊

第一作者： Halimu, Gulinare

作者： Halimu, Gulinare;Liu, Li;Zhang, Zhichun;Wang, Xiujuan;Gu, Wu;Zhang, Bowen;Dai, Yumeng;Zhang, Huiwen;Zhang, Chenggang;Xu, Mingkai;Zhang, Qianru;Zhang, Zhichun;Gu, Wu;Zhang, Bowen;Dai, Yumeng

作者机构：

关键词： Newly-emerging hazardous material; Nanoplastics; Toxicologic mechanism; Epithelial-to-mesenchymal transition

期刊名称：JOURNAL OF HAZARDOUS MATERIALS （ 影响因子：14.224； 五年影响因子：12.984 ）

ISSN： 0304-3894

年卷期： 2022 年 430 卷

页码：

收录情况： SCI

摘要： As a newly emerging hazardous material, airborne nanoplastics are easily inhaled and accumulated in human and animal alveoli. We previously found that polystyrene nanoplastics (PS-NPs) induced apoptosis and inflammation of human alveolar epithelial A549 cells, implying they increase the risk of pulmonary fibrosis. In this study, we investigated whether PS-NPs induce epithelial-to-mesenchymal transition (EMT), the prelude to lung fibrosis, in A549 cells. A549 cells treated with PS-NPs of different sizes and surface charges exhibited increased migration and EMT markers accompanied with up-regulation of reactive oxygen species (ROS) and NADPH oxidase 4 (NOX4), an ROS generator located in the mitochondria and endoplasmic reticulum (ER). Moreover, PS-NPs caused mitochondrial dysfunction as demonstrated by membrane potential changes and impaired cellular energy metabolism. PS-NPs also activated ER stress as indicated by the up-regulated ER stress markers. As expected, smaller PS-NPs with a positive surface charge had stronger effects. Furthermore, the effects of PS-NPs on A549 cells were reversed by NOX4 gene knock-down, which verified the involvement of NOX4. Our results suggest that PS-NPs induce EMT in A549 cells through multiple mechanisms, and NOX4 is a key mediator in this process. Our findings contribute to understanding the toxicological mechanisms of nanoplastics on the respiratory system.

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