PM2.5 and water-soluble components induce airway fibrosis through TGF-β1/Smad3 signaling pathway in asthmatic rats
PM2.5 and water-soluble components induce airway fibrosis through TGF-β1/Smad3 signaling pathway in asthmatic rats
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PM2.5和水溶性成分通过TGF-β1/Smad3信号通路诱导哮喘大鼠气道纤维化
DOI：
10.1016/j.molimm.2021.06.005
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发表时间：
2021
影响因子：
3.6
通讯作者：
Zhihong Zhang
中科院分区：
文献类型：
--
作者：
Hongyan Wu;Dan Wang;Hao Shi;Nannan Liu;Caihong Wang;Jiayu Tian;Xin Wang;Zhihong Zhang
流行病学研究表明，细颗粒物（PM2.5）和哮喘与肺纤维化独立相关，但很少一起研究。此外，尚不清楚哮喘中的气道纤维化是否更多地归因于PM2.5的水溶性离子。本研究旨在探讨PM2.5及水溶性成分在卵清蛋白（OVA）致敏哮喘大鼠气道纤维化中的作用机制。给大鼠气管内滴注PM2.5和水溶性成分，每3天1次，共4次或8次。组织病理学检查显示，PM2.5和水溶性成分暴露后，可引起肺组织炎症和气道纤维化。同时，PM2.5，特别是水溶性提取物，增加胶原蛋白1（COL-1）、结缔组织生长因子（CTGF）、白细胞介素-6（IL-6）、转化生长因子-β1（TGF-β1）、Smad家族成员3（Smad 3）和p-Smad 3的表达，而减少血红素加氧酶-1（HO-1）的分泌。TGF-β1抑制剂SB 432542和Smad 3拮抗剂SIS 3 HCl预处理可逆转水溶性提取物诱导的哮喘大鼠气道纤维化。因此，TGF-β1/Smad 3信号通路可能参与了PM2. 5和水溶性成分暴露后哮喘大鼠气道纤维化的病理过程。
Epidemiological studies have suggested that fine particulate matter (PM2.5) and asthma have been independently associated with pulmonary fibrosis but rarely studied together. Furthermore, it is unknown whether airway fibrosis in asthma is more attributable to water-soluble ions of PM2.5. Our current study was to explore the potential mechanism of PM2.5and water-soluble components on airway fibrosis in ovalbumin (OVA)-sensitized asthmatic rats. Rats were intratracheally instilled with PM2.5and water-soluble components every 3 days for 4 times or 8 times. Histopathological examination demonstrated that lung inflammatory and airway fibrosis were induced after PM2.5and water-soluble components exposure. Meanwhile, PM2.5, in particular water-soluble extracts, increased expression of collagen 1 (COL-1), connective tissue growth factor (CTGF), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), Smad family member 3 (Smad3), and p-Smad3, whereas decreased secretion of heme oxygenase-1 (HO-1). However, pretreating asthmatic rats with SB432542, the inhibitor of TGF-β1, and SIS3 HCl, the antagonist of Smad3, both reversed the activation of airway fibrosis induced by water-soluble extracts. Therefore, TGF-β1/Smad3 signaling pathway may be responsible for the pathological process of airway fibrosis in asthmatic rats following PM2.5and water-soluble components exposure.