Notch信号通路调控臭氧诱导的肺昼夜节律紊乱。

IF 4.1 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Toxics Pub Date : 2025-08-30 DOI:10.3390/toxics13090733

Xinyu Zhang, Xiaotong Jian, Xinyi Miao, Yangyang Jia

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引用次数: 0

摘要

背景：臭氧（O3）污染破坏肺的昼夜节律，但其分子机制尚不明确。Notch信号通路对肺内稳态至关重要，可能与生物钟系统发生串扰。目的：本研究阐明Notch信号通路在臭氧诱导的肺昼夜节律紊乱中的作用。方法：C57BL/6J小鼠急性暴露于O3 （1.0 ppm, 3 h）。暴露24 h后采集肺组织。转录组测序结合GSEA鉴定了失调通路；IHC和RT-qPCR验证核心基因；GEO数据集（GSE58244）再分析评估了Notch3/4基因敲除效应。结果：O3激活Notch信号通路（NES = 1.85, FDR = 0.034），扰乱昼夜节律通路（NES = 1.84, FDR = 0.029），下调Bmal1，上调Per2/3和Notch3/4 （p < 0.05）。两种通路的核心基因之间存在较强的相关性（r > 0.8）。Notch3/4敲除在O3暴露后以时间依赖的方式加剧了昼夜节律中断。结论：O3通过Notch3/4激活诱导肺昼夜节律紊乱，为污染物诱导的肺损伤提供了新的机制。

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Notch Signaling Pathway Regulates Ozone-Induced Lung Circadian Rhythm Disruption.

Background: Ozone (O₃) pollution disrupts pulmonary circadian rhythms, yet the molecular mechanisms remain elusive. The Notch signaling pathway, critical for lung homeostasis, may crosstalk with the circadian clock system.

Objective: This study elucidates the role of the Notch signaling pathway in O₃-induced lung circadian rhythm disruption.

Methods: C57BL/6J mice were acutely exposed to O₃ (1.0 ppm, 3 h). Lung tissues were collected 24 h post exposure. Transcriptome sequencing coupled with GSEA identified dysregulated pathways; IHC and RT-qPCR validated core genes; GEO dataset (GSE58244) reanalysis assessed Notch3/4 knockout effects.

Results: O₃ activated Notch signaling (NES = 1.85, FDR = 0.034) and disrupted the circadian pathway (NES = 1.84, FDR = 0.029), downregulating Bmal1 while upregulating Per2/3 and Notch3/4 (p < 0.05). Strong correlations (r > 0.8) existed between core genes of both pathways. Notch3/4 knockout exacerbated circadian disruption in a time-dependent manner upon O₃ exposure.

Conclusion: O₃ induces lung circadian disruption via Notch3/4 activation, which provides novel mechanistic insights into pollutant-induced lung injury.

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来源期刊

Toxics Chemical Engineering-Chemical Health and Safety

CiteScore

4.50

自引率

10.90%

发文量

681

审稿时长

6 weeks

期刊介绍： Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.