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.

中文翻译：

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miR-629-3p 抑制细颗粒物暴露诱导的肺功能下降：两阶段人群研究和体外研究的结果


据报道，MiRNAs 在环境污染物引起的健康损害的发病机制中起着关键作用。然而，它在细颗粒物 （PM _2.5 ） 暴露诱导的肺功能下降中的潜在作用很少被阐明。本研究旨在分析与 PM _2.5 暴露和肺功能下降相关的特异性 miRNA，并探讨在 PM _2.5 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，通过下一代测序对 60 名参与者进行 PM _2.5 暴露的血浆 miRNA 分析，其中 120 名观察采用重复测量设计。在 10 对肺功能下降事件病例中进行肺功能下降的血浆 miRNA 分析，并与健康对照者相匹配。在验证阶段，从与 PM _2.5 暴露和肺功能下降相关的 miRNA 中选择 miR-629-3p，并通过 475 名居民的定量实时 PCR 进行测量，以验证其与 PM _2.5 暴露和肺功能的关联。在体外，使用 PM _2.5 处理的 A549 和 BEAS-2B 细胞模型以及 miR-629-3p 模拟物/抑制剂模型来探索 miR-629-3p 对 PM _2.5 暴露诱导的上皮-间充质转化 （EMT） 的作用和潜在机制。两阶段人群研究发现，个人 PM _2.5 暴露与血浆 miR-629-3p 呈负相关，而 miR-629-3p 与肺功能呈正相关。体外，PM _2.5 治疗刺激 EMT 相关因子的表达，并伴有 TGF-β1/TGF-βR1 信号通路的激活。 过表达 miR-629-3p 可抑制 PM _2.5 诱导的 TGF-βR1 表达并减轻 EMT 过程。抑制 miR-629-3p 可促进 TGF-βR1 表达并加重 EMT 过程。综上所述，miR-629-3p 可能通过抑制 TGF-β1/TGF-βR1 通路减轻 PM _2.5 暴露诱导的肺损伤。