Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Respiratory Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Biomed Pharmacother. 2016 Oct;83:514-520. doi: 10.1016/j.biopha.2016.07.007. Epub 2016 Jul 18.
Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH). Pulmonary arterial smooth muscle cells (PASMCs) play a critical role in the pathogenesis of PAH-associated arterial remodeling. This study was done to explore the expression and biological roles of periostin in PASMCs following exposure to cigarette smoke extract (CSE). PASMCs were exposed to different concentrations of CSE and tested for gene expression and reactive oxygen species (ROS) production. PASMCs were incubated with recombinant periostin protein or transfected with small interfering RNA targeting periostin before CSE exposure and then examined for cell proliferation and migration. Compared to control cells, exposure to CSE led to a significant upregulation of periostin. Pretreatment with 5mM N-acetyl-l-cysteine (an inhibitor of ROS formation) or 10μM U0126 (an inhibitor of ERK1/2) significantly prevented the induction of periostin in CSE-treated PASMCs. The addition of recombinant periostin protein significantly enhanced the proliferation and migration of PASMCs. In contrast, knockdown of endogenous periostin counteracted the proliferation and migration of PASMCs induced by CSE treatment. In conclusion, CSE induces the expression of periostin in PASMCs via promotion of ROS and activation of ERK1/2. Periostin mediates the effects of CSE on PASMC proliferation and migration. These findings warrant further exploration of the roles of periostin in cigarette smoking-associated pulmonary arterial remodeling.
吸烟是肺动脉高压（PAH）的一个重要危险因素。肺动脉平滑肌细胞（PASMCs）在 PAH 相关动脉重构的发病机制中起着关键作用。本研究旨在探讨在暴露于香烟烟雾提取物（CSE）后，骨膜蛋白（Periostin）在 PASMCs 中的表达及其生物学作用。将 PASMCs 暴露于不同浓度的 CSE 中，并检测其基因表达和活性氧（ROS）产生情况。在暴露于 CSE 之前，用重组骨膜蛋白蛋白或针对骨膜蛋白的小干扰 RNA 转染 PASMCs，然后检测细胞增殖和迁移情况。与对照细胞相比，暴露于 CSE 导致骨膜蛋白的表达显著上调。用 5mM N-乙酰-L-半胱氨酸（ROS 形成抑制剂）或 10μM U0126（ERK1/2 抑制剂）预处理可显著阻止 CSE 处理的 PASMCs 中骨膜蛋白的诱导。添加重组骨膜蛋白蛋白显著增强了 PASMCs 的增殖和迁移。相反，内源性骨膜蛋白的敲低抵消了 CSE 处理诱导的 PASMCs 的增殖和迁移。总之，CSE 通过促进 ROS 和激活 ERK1/2 诱导 PASMCs 中骨膜蛋白的表达。骨膜蛋白介导了 CSE 对 PASMC 增殖和迁移的影响。这些发现需要进一步探讨骨膜蛋白在吸烟相关肺动脉重构中的作用。
