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

Authors :
Zheng, Lulu
Wang, Yuwen
Zhang, Yule
Fu, Yongfeng
Yang, Zhijin
Fan, Yan
Sun, Zhen
Zhao, Mantong
Zhu, Lijun
Dai, Bo
An, Dong
Zhang, Dawei
Liu, Sixiu
Source :
Science of the Total Environment. Mar2021, Vol. 761, pN.PAG-N.PAG. 1p.
Publication Year :
2021

Abstract

Air pollution has side effects on human health. Epidemiology studies indicate a positive association between ambient fine particle (PM 2.5 , or particles less than 2.5 μm 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 PM 2.5 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 PM 2.5 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/PLCγ and EGFR/STAT/Bcl-XL pathways after PM 2.5 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 PM 2.5 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. Unlabelled Image • A small air–liquid interface microfluidic system that mimics lung functions for cells exposure • EGFR gene expression change after PM 2.5 exposure was the result of the alteration of DNA methylome. • EGFR gene regulates calcium flux via the EGFR/PLCγ pathways after PM 2.5 exposure. • EGFR gene regulates apoptosis via the EGFR/STAT/Bcl-XL pathways after PM 2.5 exposure. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00489697
Volume :
761
Database :
Academic Search Index
Journal :
Science of the Total Environment
Publication Type :
Academic Journal
Accession number :
148126022
Full Text :
https://doi.org/10.1016/j.scitotenv.2020.143200