PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/β-Catenin Pathway.
PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/β-Catenin Pathway.
复制标题
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
复制
发表时间：
2021
影响因子：
2.8
通讯作者：
Ran P
中科院分区：
文献类型：
--
作者：
Zou W;Wang X;Sun R;Hu J;Ye D;Bai G;Liu S;Hong W;Guo M;Ran P
细颗粒物≤2.5 μm直径（PM2.5）相关的气道重塑最近被认为是COPD的核心特征。Wnt/β-catenin通路的激活与气道重塑的发生密切相关。因此，本研究的目的是确定Wnt5a/β-Catenin通路是否参与pm2.5诱导的体内和体外平滑肌增殖，从而促进COPD受试者气道重塑的发展。通过体外pm2.5诱导的COPD和pm2.5暴露的人支气管平滑肌细胞（HBSMCs）体内模型，评估Wnt5a对β- catenin介导的气道重塑的影响。采用小动物肺活量法测定小鼠肺功能。H&E染色及免疫组化检查肺气肿及气道重塑指标。采用Real-time PCR检测Wnt5a、β-Catenin、TGF-β1、CyclinD1、c-myc mRNA的表达。CCK8法检测细胞活性。Western blotting检测PCNA、α-SMA、Wnt5a、β-Catenin、PDGFRβ和TenascinC蛋白的表达。细胞免疫荧光法检测β-Catenin的表达。PM2.5暴露导致小鼠肺组织中肺气肿、气道壁增厚、平滑肌层厚度增加、肺功能下降、Wnt5a、β-Catenin、PDGFRβ和Tenascin C蛋白表达增加。BOX5（一种Wnt5a拮抗剂）在小鼠中减轻了这些pm2.5诱导的结果。PM2.5可诱导HBSMCs中Wnt5a、β-Catenin、TGF-β1、CyclinD1和c-myc mrna的表达。BOX5还能抑制pm2.5诱导的HBSMCs中PCNA、α-SMA、Wnt5a、β-Catenin、PDGFRβ和Tenascin C蛋白表达的升高。我们的研究结果表明，PM2.5暴露诱导HBSMC增殖，通过体内和体外的Wnt5a/β-Catenin信号通路促进气道重塑，这可能是COPD治疗的靶点。
Fine-particulate matter ≤2.5 μm in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/β-Catenin pathway is involved in PM2.5-induced smooth muscle proliferation in vivo and in vitro, which promotes the development of airway remodeling in subjects with COPD. The effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cells (HBSMCs) in vitro. Small animal spirometry was used to measure lung function in mice. H&E staining and immunohistochemistry were performed to inspect emphysema and airway remodeling indices. Real-time PCR was used to detect Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. β-Catenin expression was detected using cellular immunofluorescence. Exposure to PM2.5 led to emphysema, airway wall thickening, an increased smooth muscle layer thickness, decreased lung function and increased expression of the Wnt5a, β-Catenin, PDGFRβ and Tenascin C proteins in the mouse lung tissue. BOX5 (a Wnt5a antagonist) alleviated these PM2.5-induced outcomes in mice. Moreover, PM2.5 induced the expression of the Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMCs. Our findings suggest that PM2.5 exposure induces HBSMC proliferation, contributing to airway remodeling via the Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.