PM2.5 通过 sonic hedgehog 信号通路促进人支气管平滑肌细胞迁移。
PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.
机构信息
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xiamen Humanity Hospital, Xiamen, Fujian, China.
出版信息
Respir Res. 2018 Mar 2;19(1):37. doi: 10.1186/s12931-017-0702-y.
BACKGROUND
The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways.
METHODS
HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression.
RESULTS
PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail.
CONCLUSIONS
These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.
背景
慢性阻塞性肺疾病（COPD）中气道重塑的作用已得到充分证实，气道平滑肌细胞增殖和迁移在重塑过程中起作用。在这里，我们旨在验证细颗粒物（PM2.5）对人支气管平滑肌细胞（HBSMC）迁移的影响，并探讨潜在的信号通路。
方法
通过流式细胞术、细胞计数和 Transwell 迁移实验分别测量 HBSMC 凋亡、增殖和迁移。通过 Western blot 测量 Sonic hedgehog (Shh)、Gli1 和 Snail 的表达来评估 hedgehog 通路在细胞迁移中的作用。此外，使用 siRNA 敲低 Gli1 或 Snail 的表达。
结果
PM2.5 呈剂量依赖性诱导 HBSMC 凋亡，但某些浓度的 PM2.5 不会诱导 HBSMC 增殖或凋亡。有趣的是，细胞迁移是由远低于诱导凋亡的 PM2.5 剂量刺激的。进一步的实验表明，这些 PM2.5 剂量增强了 HBSMC 中 Shh、Gli1 和 Snail 的表达。此外，PM2.5 诱导的细胞迁移和蛋白表达通过重组 Shh 增强，并通过环巴胺减弱。敲低 Gli1 或 Snail 也得到了类似的结果。
结论
这些发现表明，PM2.5 可能通过 Shh 信号通路发挥作用，是 HBSMC 迁移所必需的。这些数据定义了 PM2.5 在 COPD 气道重塑中的新作用。
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