miR-629-3p inhibits fine particulate matter exposure-induced lung function decline: results from the two-stage population study and in vitro study

IF 7.6 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Pollution Pub Date : 2024-12-17 DOI:10.1016/j.envpol.2024.125535

Min Zhou, Xiaojie You, Jiake Zhang, Zi Ye, Jiahao Song, Bingdong Chen, Lieyang Fan, Jixuan Ma, Shijie Yang, Man Cheng, Weihong Chen

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Abstract

MiRNAs were reported to play crucial roles in the pathogenesis of health damage caused by environmental pollutants. However, its potential role in fine particulate matter (PM_2.5) exposure-induced lung function decline has rarely been elucidated. The present study was developed to profile specific miRNAs that were related to both PM_2.5 exposure and lung function decline, and to investigate the regulating role in PM_2.5 exposure-induced lung injury. Based on the Wuhan-Zhuhai cohort, in the discovery stage, plasma miRNA profiling for PM_2.5 exposure was conducted through next-generation sequencing among 60 participants with 120 observations in a repeated-measures design. Plasma miRNA profiling for lung function decline was conducted among 10 pairs of lung function decline incident cases and matched healthy controls. In the validating stage, miR-629-3p was selected from miRNAs that were related to both PM_2.5 exposure and lung function decline, and was measured by quantitative real-time PCR among 475 residents to validate its association with PM_2.5 exposure as well as lung function. In vitro, PM_2.5-treated A549 and BEAS-2B cell models and miR-629-3p mimic/inhibitor models were used to explore the role and underlying mechanism of miR-629-3p on epithelial-mesenchymal transition (EMT) induced by PM_2.5 exposure. The two-stage population study found a negative association between personal PM_2.5 exposure and plasma miR-629-3p, while a positive association between miR-629-3p and lung function. In vitro, PM_2.5 treatment stimulated the expressions of EMT-related factors, accompanied by the activation of TGF-β1/TGF-βR1 signal pathway. Overexpression of miR-629-3p could inhibit PM_2.5-induced TGF-βR1 expression and alleviate EMT process. And inhibition of miR-629-3p could promote TGF-βR1 expression and aggravate EMT process. In conclusion, miR-629-3p may alleviate the lung injury induced by PM_2.5 exposure through inhibiting TGF-β1/TGF-βR1 pathway.

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据报道，MiRNA 在环境污染物造成健康损害的发病机制中发挥着至关重要的作用。然而，其在细颗粒物（PM2.5）暴露引起的肺功能下降中的潜在作用却很少被阐明。本研究旨在分析与PM2.5暴露和肺功能下降均相关的特定miRNA，并探讨其在PM2.5暴露诱导的肺损伤中的调节作用。本研究以武汉-珠海队列为基础，在发现阶段通过新一代测序技术对 60 名参与者进行了血浆 miRNA 分析，共观察 120 次，采用重复测量设计。对 10 对肺功能下降的病例和匹配的健康对照组进行了血浆 miRNA 分析。在验证阶段，研究人员从与PM2.5暴露和肺功能下降均相关的miRNA中挑选了miR-629-3p，并在475名居民中通过实时定量PCR进行了测定，以验证其与PM2.5暴露和肺功能的关系。在体外，研究人员利用经PM2.5处理的A549和BEAS-2B细胞模型以及miR-629-3p模拟物/抑制剂模型，探讨了miR-629-3p在PM2.5暴露诱导的上皮-间质转化（EMT）中的作用及其内在机制。两阶段人群研究发现，个人PM2.5暴露与血浆miR-629-3p呈负相关，而miR-629-3p与肺功能呈正相关。在体外，PM2.5处理刺激了EMT相关因子的表达，同时激活了TGF-β1/TGF-βR1信号通路。过表达 miR-629-3p 可抑制 PM2.5 诱导的 TGF-βR1 表达，缓解 EMT 过程。而抑制 miR-629-3p 则会促进 TGF-βR1 的表达，加重 EMT 过程。总之，miR-629-3p 可通过抑制 TGF-β1/TGF-βR1 通路减轻 PM2.5 暴露诱导的肺损伤。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.