Epidemiological evidence has shown that fine particulate matter (PM_2.5)-triggered inflammatory cascades are pivotal causes of chronic obstructive pulmonary disease (COPD). However, the specific molecular mechanism involved in PM_2.5-induced COPD has not been clarified. Herein, we found that PM_2.5 significantly downregulated miR-149-5p and activated the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and generated the inflammatory response in COPD mice and in human bronchial epithelial (BEAS-2B) cells. We determined that increased expression of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) induced by PM_2.5 was associated with decreased expression of miR-149-5p. The loss- and gain-of-function approach further confirmed that miR-149-5p could inhibit PM_2.5-induced cell inflammation in BEAS-2B cells. The double luciferase reporter assay showed that miR-149-5p directly targeted TGF-beta-activated kinase 1 binding protein 2 (TAB2), which regulates the MAPK and NF-κB signaling pathways. We showed that miR-149-5p mediated the inflammatory response by targeting the 3′-UTR sequence of TAB2 and that it subsequently weakened the TAB2 promotor effect via the MAPK and NF-κB signaling pathways in BEAS-2B cells exposed to PM_2.5. Thus, miR-149-5p may be a key factor in PM_2.5-induced COPD. This study improves our understanding of the molecular mechanism of COPD.

Graphical abstract

中文翻译：

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microRNA-149-5p 在体内和体外通过 MAPK 和 NF-κB 信号通路靶向 TAB2 介导 PM2.5 诱导的炎症反应

流行病学证据表明，细颗粒物 (PM _2.5 ) 引发的炎症级联反应是慢性阻塞性肺病 (COPD) 的关键原因。_{然而，PM 2.5}诱发COPD的具体分子机制尚未阐明。在此，我们发现 PM _2.5显着下调 miR-149-5p，激活丝裂原激活蛋白激酶 (MAPK) 和核因子 -κ B (NF-κB) 信号通路，并在 COPD 小鼠和人支气管中产生炎症反应。上皮细胞（BEAS-2B）。_{我们确定，PM 2.5}诱导的白细胞介素-1β (IL-1β)、IL-6、IL-8 和肿瘤坏死因子-α (TNF-α) 表达增加与 miR-149-5p 表达减少相关。功能丧失和获得方法进一步证实 miR-149-5p 可以抑制BEAS-2B 细胞中PM _{2.5诱导的细胞炎症。}双荧光素酶报告基因检测显示，miR-149-5p 直接靶向 TGF-β 激活激酶 1 结合蛋白 2 ( TAB2 )，该蛋白调节 MAPK 和 NF-κB 信号通路。_{我们发现，在暴露于 PM 2.5}的 BEAS-2B 细胞中， miR-149-5p 通过靶向TAB2的 3'-UTR 序列介导炎症反应，并随后通过 MAPK 和 NF-κB 信号通路削弱TAB2启动子效应。_{因此，miR-149-5p可能是PM 2.5}诱导的COPD的关键因素。这项研究增进了我们对COPD分子机制的理解。

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