EGFR inhibitors regulate Ca2+ concentration and apoptosis after PM2.5 exposure based on a lung-mimic microfluidic system

文献类型： 外文期刊

第一作者： Zheng, Lulu

作者： Zheng, Lulu;Wang, Yuwen;Zhang, Yule;Yang, Zhijin;Fan, Yan;Zhao, Mantong;Dai, Bo;Zhang, Dawei;An, Dong;Liu, Sixiu;Zhang, Dawei;Fu, Yongfeng;Zhu, Lijun;Sun, Zhen

作者机构：

关键词： PM2.5; DNA methylation; Transcriptomic (RNA-Seq); Ca2+ concentration; Apoptosis

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：7.963； 五年影响因子：7.842 ）

ISSN： 0048-9697

年卷期： 2021 年 761 卷

页码：

收录情况： SCI

摘要： Air pollution has side effects on human health. Epidemiology studies indicate a positive association between ambient fine particle (PM2.5, or particles less than 2.5 mu m in diameter) concentration and lung cancer. However, how fine particles affect lung cancer at the molecular level and related therapeutic methods to address these diseases are unclear. Here, the multi-omics analysis (DNA methylation and transcriptomic) was used to detect human bronchial epithelial cells (HBE), that were exposed to PM2.5 using a quantified, small, portable, and organ-level air-liquid interface microfluidic system that mimics lung functions. The results indicate that 36,838 differentially methylated genes were detected. Of these 33,796 genes were hypomethylated (beta < 0), and 2862 genes were hypermethylated (beta > 0). RNA-Seq analysis demonstrated that 19,489 genes were upregulated (log(2)FC > 0), and 16,659 were downregulated. Furthermore, the calcium and apoptosis pathways were activated according to multi-omics analysis. The change in EGFR gene expression after PM2.5 exposure was the result of alterations of the cellular DNA methylome in the promoter. Inhibition or down-regulation of EGFR could result in the regulation of the downstream intracellular Ca2+ concentration and apoptosis via the EGFR/PLC gamma and EGFR/STAT/Bcl-XL pathways after PM2.5 exposure. EGFR inhibitors decrease the Ca2+ concentration of cells, thereby strengthening the effects of fine particles on apoptosis. In short, the Ca2+ concentration and the apoptosis of cells can be regulated via EGFR related pathway after PM2.5 exposure. The EGFR may be a potentially promising therapeutic target for the treatment of air pollution-induced lung cancer through regulation of the intracellular Ca2+ concentration and apoptosis. (C) 2020 Published by Elsevier B.V.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序