PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.
PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.
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PM2.5通过声波刺猬信号通路促进人支气管平滑肌细胞迁移
DOI：
10.1186/s12931-017-0702-y
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发表时间：
2018-03-02
影响因子：
5.8
通讯作者：
Ran P
中科院分区：
文献类型：
--
作者：
Ye X;Hong W;Hao B;Peng G;Huang L;Zhao Z;Zhou Y;Zheng M;Li C;Liang C;Yi E;Pu J;Li B;Ran P
背景：气道重塑在慢性阻塞性肺疾病（COPD）中的作用已被充分证实，气道平滑肌细胞增殖和迁移在重塑过程中发挥作用。在这里，我们的目的是验证细颗粒物（PM2.5）对人支气管平滑肌细胞（HBSMC）迁移的影响，并探讨潜在的信号转导途径。方法：HBSMC凋亡，增殖和迁移分别采用流式细胞术，细胞计数和transwell迁移实验。hedgehog通路在细胞迁移中的作用通过蛋白质印迹法来评估，以测量Sonic hedgehog（Shh）、Gli1和Snail的表达。结果：PM2.5以剂量依赖的方式诱导HBSMC凋亡，但一定浓度的PM2.5不能诱导HBSMC增殖或凋亡。有趣的是，PM2.5剂量远低于诱导细胞凋亡的剂量刺激细胞迁移。另外的实验表明，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增强重组Shh和衰减环巴胺。通过敲低Gli1或Snail.Conclusions获得了类似的结果：这些发现表明，PM2.5，这可能是通过Shh信号通路发挥其作用，是必要的HBSMCs的迁移。这些数据定义了PM2.5在COPD气道重塑中的新作用。
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.
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影响因子：
4.6
作者：
Huang L;Pu J;He F;Liao B;Hao B;Hong W;Ye X;Chen J;Zhao J;Liu S;Xu J;Li B;Ran P
通讯作者：
Ran P
影响因子：
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作者：
Nagase, Takashi;Nagase, Miki;Fujita, Toshiro
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影响因子：
4.6
作者：
Mahmood MQ;Walters EH;Shukla SD;Weston S;Muller HK;Ward C;Sohal SS
通讯作者：
Sohal SS
影响因子：
8.8
作者：
Ohta, H.;Aoyagi, K.;Fukaya, M.;Danjoh, I.;Ohta, A.;Isohata, N.;Saeki, N.;Taniguchi, H.;Sakamoto, H.;Shimoda, T.;Tani, T.;Yoshida, T.;Sasaki, H.
通讯作者：
Sasaki, H.