PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway.
PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway.
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PM2.5 通过 Wnt5a/JNK 通路的气道平滑肌细胞表达诱导肺部炎症和纤维化。
DOI：
10.21037/jtd-23-780
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发表时间：
2023-11-30
影响因子：
2.5
通讯作者：
Ran, Pixin
中科院分区：
文献类型：
--
作者：
Zou, Weifeng;Liu, Shuling;Ye, Dong;Bai, Ge;Guo, Meihua;Sun, Ruiting;Ran, Pixin
关键词：
近年来，颗粒物2.5（PM2.5）暴露被认为是慢性阻塞性肺疾病（COPD）的关键危险因素。COPD患者气道平滑肌细胞（ASMCs）的功能障碍促进了肺的炎症和纤维化。因此，本研究探讨了PM2. 5是否通过Wnt 5a/JNK/NF-κB细胞轻链增强子（nuclear factor kappa-light-chain-enhancer of activated B cells，NF-κB）途径促进ASMCs的炎症反应和纤维化。采用酶联免疫吸附试验（ELISA）检测暴露于PM2.5的COPD患者支气管肺泡灌洗液（BALF）中Wnt 5a的表达。小鼠气管内注射PM2.5和Wnt 5a拮抗剂（BOX 5）。在PM2.5刺激之前，用Wnt 5a小干扰RNA（siRNA）、BOX 5和JNK抑制剂SP 600125转染ASMCs。进行苏木精和伊红（H&E）染色以测量炎症反应和气道纤维化。通过Western印迹分析Wnt 5a/JNK/NF-κ B途径因子的产生。ELISA法检测IL-6、IL-8和TNF-α的分泌。通过定量真实的时间聚合酶链反应（qRT-PCR）和蛋白质印迹法评估α平滑肌肌动蛋白（α-SMA）、胶原I和胶原III的表达水平。我们发现COPD患者BALF中Wnt 5a表达的增加与PM2.5暴露水平呈正相关。PM2. 5诱导的模型小鼠和PM2. 5暴露的ASMCs肺组织中Wnt 5a/JNK/NF-κB通路被激活，促进α-SMA、I型胶原和III型胶原的合成，增加IL-6、IL-8和TNF-α的分泌。此外，我们的研究结果表明，BOX 5可以防止这些影响。Wnt 5a siRNA阻断了Wnt 5a/JNK/NF-κB通路的激活，抑制了PM2. 5对ASMCs纤维化和炎症的影响。SP 600125可阻断NF-κB的磷酸化，抑制PM2.5暴露ASMCs的炎症和纤维化。这些结果表明，PM2.5刺激ASMCs通过Wnt 5a/JNK通路诱导COPD期间肺炎症因子表达和胶原沉积，这表明调节Wnt 5a/JNK通路可能是PM2.5诱导的COPD的有希望的治疗策略。
In recent years, particulate matter 2.5 (PM2.5) exposure has been considered a key dangerous factor in chronic obstructive pulmonary disease (COPD). The dysfunction of airway smooth muscle cells (ASMCs) facilitates lung inflammation and fibrosis in COPD. Therefore, we explored whether PM2.5 could promote the inflammatory response and fibrosis in ASMCs in vivo and in vitro via the wingless-related integration site 5a (Wnt5a)/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Wnt5a expression in the bronchoalveolar lavage fluid (BALF) of COPD patients exposed to PM2.5 was measured by enzyme-linked immunosorbent assay (ELISA). Mice were intratracheally injected with PM2.5 and a Wnt5a antagonist (BOX5). ASMCs were transfected with Wnt5a small interfering RNA (siRNA), BOX5 and the JNK inhibitor SP600125 before PM2.5 stimulation. Hematoxylin and eosin (H&E) staining was performed to measure the inflammatory response and airway fibrosis. The production of Wnt5a/JNK/NF-KB pathway factors was analyzed by Western blotting. The secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) was measured by ELISA. The expression levels of alpha smooth muscle actin (α-SMA), collagen I and collagen III were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. We found that the increase in Wnt5a expression in the BALF of COPD patients was positively correlated with the levels of PM2.5 exposure. The Wnt5a/JNK/NF-κB pathway was activated in the lung samples of PM2.5-induced model mice and PM2.5-exposed ASMCs, which promoted the production of α-SMA, collagen I and collagen III and increased the secretion of IL-6, IL-8 and TNF-α. Furthermore, our results showed that BOX5 could prevent these effects. Wnt5a siRNA blocked the activation of the Wnt5a/JNK/NF-κB pathway and inhibited the effects of PM2.5 on fibrosis and inflammation in ASMCs. SP600125 blocked the phosphorylation of NF-κB and inhibited inflammation and fibrosis in PM2.5-exposed ASMCs. These findings suggest that PM2.5 stimulation of ASMCs induces pulmonary inflammatory factor expression and collagen deposition during COPD via the Wnt5a/JNK pathway, which indicates that modulating the Wnt5a/JNK pathway could be a promising therapeutic strategy for PM2.5-induced COPD.
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影响因子：
4.1
作者：
Popmihajlov Z;Sutherland DJ;Horan GS;Ghosh A;Lynch DA;Noble PW;Richeldi L;Reiss TF;Greenberg S
通讯作者：
Greenberg S
影响因子：
7.4
作者：
Yan F;Gao H;Zhao H;Bhatia M;Zeng Y
通讯作者：
Zeng Y
1,25-二羟基维生素D3对暴露于直径小于2.5微米的空气污染物颗粒的大鼠预防慢性阻塞性肺疾病（COPD）的影响（PM2.5）。
DOI：
10.12659/msm.905509
发表时间：
2018-01-18
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Chen L;Yuan X;Zou L;Peng J;Hu X
通讯作者：
Hu X
DOI：
10.1016/j.bbrc.2018.09.070
发表时间：
2018-10-28
影响因子：
3.1
作者：
Zhu, Zhen;Yin, Shaojun;Song, Shuang
通讯作者：
Song, Shuang
PM2.5 通过 Wnt5a/β-连环蛋白途径诱导慢性阻塞性肺疾病的气道重塑。
DOI：
10.2147/copd.s334439
发表时间：
2021
影响因子：
2.8
作者：
Zou W;Wang X;Sun R;Hu J;Ye D;Bai G;Liu S;Hong W;Guo M;Ran P
通讯作者：
Ran P