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3D 原代人呼吸道培养物暴露于香烟烟雾和电子尼古丁输送系统(ENDS)制剂后的差异基因表达。

Differential gene expression of 3D primary human airway cultures exposed to cigarette smoke and electronic nicotine delivery system (ENDS) preparations.

机构信息

Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH, 43210, USA.

RAI Services Company, Winston-Salem, NC, USA.

出版信息

BMC Med Genomics. 2022 Apr 3;15(1):76. doi: 10.1186/s12920-022-01215-x.

Abstract

BACKGROUND

Acute exposure to cigarette smoke alters gene expression in several biological pathways such as apoptosis, immune response, tumorigenesis and stress response, among others. However, the effects of electronic nicotine delivery systems (ENDS) on early changes in gene expression is relatively unknown. The objective of this study was to evaluate the early toxicogenomic changes using a fully-differentiated primary normal human bronchial epithelial (NHBE) culture model after an acute exposure to cigarette and ENDS preparations.

RESULTS

RNA sequencing and pathway enrichment analysis identified time and dose dependent changes in gene expression and several canonical pathways when exposed to cigarette preparations compared to vehicle control, including oxidative stress, xenobiotic metabolism, SPINK1 general cancer pathways and mucociliary clearance. No changes were observed with ENDS preparations containing up to 28 µg/mL nicotine. Full model hierarchical clustering revealed that ENDS preparations were similar to vehicle control.

CONCLUSION

This study revealed that while an acute exposure to cigarette preparations significantly and differentially regulated many genes and canonical pathways, ENDS preparations containing the same concentration of nicotine had very little effect on gene expression in fully-differentiated primary NHBE cultures.

摘要

背景

急性暴露于香烟烟雾会改变细胞凋亡、免疫反应、肿瘤发生和应激反应等多个生物途径中的基因表达。然而,电子尼古丁输送系统(ENDS)对基因表达早期变化的影响尚不清楚。本研究的目的是使用完全分化的原代正常人类支气管上皮(NHBE)培养模型,评估急性暴露于香烟和 ENDS 制剂后早期的毒代基因组变化。

结果

与载体对照组相比,RNA 测序和通路富集分析发现,暴露于香烟制剂后,基因表达和几个经典通路(包括氧化应激、外源性代谢物、SPINK1 一般癌症通路和黏液纤毛清除)存在时间和剂量依赖性变化。而含有高达 28μg/ml 尼古丁的 ENDS 制剂则没有观察到变化。全模型层次聚类显示,ENDS 制剂与载体对照组相似。

结论

本研究表明,尽管急性暴露于香烟制剂会显著且差异地调节许多基因和经典通路,但含有相同浓度尼古丁的 ENDS 制剂对完全分化的原代 NHBE 培养物中的基因表达影响很小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfd/8978419/c931bb399999/12920_2022_1215_Fig1_HTML.jpg

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