EGFR inhibitors regulate Ca2+ concentration and apoptosis after PM2.5 exposure based on a lung-mimic microfluidic system.
Abstract
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 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 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 (log2FC > 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 intrace...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis