Zhou Min, You Xiaojie, Zhang Jiake, Ye Zi, Song Jiahao, Chen Bingdong, Fan Lieyang, Ma Jixuan, Yang Shijie, Cheng Man, Chen Weihong
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei, 430079, China.
Environ Pollut. 2025 Feb 15;367:125535. doi: 10.1016/j.envpol.2024.125535. Epub 2024 Dec 17.
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) exposure-induced lung function decline has rarely been elucidated. The present study was developed to profile specific miRNAs that were related to both PM exposure and lung function decline, and to investigate the regulating role in PM exposure-induced lung injury. Based on the Wuhan-Zhuhai cohort, in the discovery stage, plasma miRNA profiling for PM 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 exposure and lung function decline, and was measured by quantitative real-time PCR among 475 residents to validate its association with PM exposure as well as lung function. In vitro, PM-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 exposure. The two-stage population study found a negative association between personal PM exposure and plasma miR-629-3p, while a positive association between miR-629-3p and lung function. In vitro, PM 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-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 exposure through inhibiting TGF-β1/TGF-βR1 pathway.
据报道，微小RNA（miRNAs）在环境污染物导致健康损害的发病机制中起关键作用。然而，其在细颗粒物（PM）暴露引起的肺功能下降中的潜在作用鲜有阐明。本研究旨在剖析与PM暴露和肺功能下降均相关的特定miRNAs，并探讨其在PM暴露诱导的肺损伤中的调节作用。基于武汉-珠海队列，在发现阶段，采用重复测量设计，对60名参与者进行了120次观察，通过下一代测序对PM暴露进行血浆miRNA分析。对10对肺功能下降发病病例和匹配的健康对照进行了肺功能下降的血浆miRNA分析。在验证阶段，从与PM暴露和肺功能下降均相关的miRNAs中选择miR-629-3p，并在475名居民中通过定量实时PCR进行检测，以验证其与PM暴露以及肺功能的关联。在体外，使用PM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miR-629-3p对PM暴露诱导的上皮-间质转化（EMT）的作用及潜在机制。两阶段人群研究发现个人PM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，PM处理刺激了EMT相关因子的表达，同时伴有TGF-β1/TGF-βR1信号通路的激活。miR-629-3p的过表达可抑制PM诱导的TGF-βR1表达并减轻EMT过程。而抑制miR-629-3p可促进TGF-βR1表达并加重EMT过程。总之，miR-629-3p可能通过抑制TGF-β1/TGF-βR1通路减轻PM暴露诱导的肺损伤。
