Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Environ Pollut. 2023 Jun 15;327:121506. doi: 10.1016/j.envpol.2023.121506. Epub 2023 Mar 28.
The effect of PM exposure on lung function reduction has been well-documented, but the underlying mechanism remains unclear. MiR-4301 may be involved in regulating pathways related to lung injury/repairment, and this study aimed to explore the potential role of miR-4301 in PM exposure-associated lung function reduction. A total of 167 Wuhan community nonsmokers were included in this study. Lung function was measured and personal PM exposure moving averages were evaluated for each participant. Plasma miRNA was determined by real-time polymerase chain reaction. A generalized linear model was conducted to assess the relationships among personal PM moving average concentrations, lung function, and plasma miRNA. The mediation effect of miRNA on the association of personal PM exposure with lung function reduction was estimated. Finally, we performed pathway enrichment analysis to predict the underlying pathways of miRNA in lung function reduction from PM exposure. We found that each 10 μg/m increase in the 7-day personal PM moving average concentration (Lag0-7) was related to a 46.71 mL, 1.15%, 157.06 mL/s, and 188.13 mL/s reductions in FEV, FEV/FVC, PEF, and MMF, respectively. PM exposure was negatively associated with plasma miR-4301 expression levels in a dose‒response manner. Additionally, each 1% increase in miR-4301 expression level was significantly associated with a 0.36 mL, 0.01%, 1.14 mL/s, and 1.28 mL/s increases in FEV, FEV/FVC, MMF, and PEF, respectively. Mediation analysis further revealed that decreased miR-4301 mediated 15.6% and 16.8% of PM exposure-associated reductions in FEV/FVC and MMF, respectively. Pathway enrichment analyses suggested that the wingless related-integration site (Wnt) signaling pathway might be one of the pathways regulated by miR-4301 in the reduction of lung function from PM exposure. In brief, personal PM exposure was negatively associated with plasma miR-4301 or lung function in a dose‒response manner. Moreover, miR-4301 partially mediated the lung function reduction associated with PM exposure.
PM 暴露对肺功能下降的影响已有充分的记录，但潜在的机制仍不清楚。miR-4301 可能参与调节与肺损伤/修复相关的途径，本研究旨在探讨 miR-4301 在 PM 暴露相关的肺功能下降中的潜在作用。共纳入 167 名武汉社区非吸烟者，对每位参与者进行肺功能测量和个人 PM 暴露移动平均值评估。通过实时聚合酶链反应测定血浆 miRNA。采用广义线性模型评估个人 PM 移动平均值浓度、肺功能和血浆 miRNA 之间的关系。估计 miRNA 对个人 PM 暴露与肺功能下降之间关联的中介效应。最后，我们进行了途径富集分析，以预测 miRNA 在 PM 暴露导致肺功能下降中的潜在途径。我们发现，个人 PM 移动平均值浓度（Lag0-7）每增加 10μg/m，FEV、FEV/FVC、PEF 和 MMF 分别降低 46.71mL、1.15%、157.06mL/s 和 188.13mL/s。PM 暴露与血浆 miR-4301 表达水平呈负相关，呈剂量反应关系。此外，miR-4301 表达水平每增加 1%，FEV、FEV/FVC、MMF 和 PEF 分别增加 0.36mL、0.01%、1.14mL/s 和 1.28mL/s。中介分析进一步表明，miR-4301 降低解释了 FEV/FVC 和 MMF 与 PM 暴露相关下降的 15.6%和 16.8%。途径富集分析表明，Wnt 信号通路可能是 miR-4301 调节 PM 暴露导致肺功能下降的途径之一。总之，个人 PM 暴露与血浆 miR-4301 或肺功能呈负相关，呈剂量反应关系。此外，miR-4301 部分介导了与 PM 暴露相关的肺功能下降。
