• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells
【24h】

Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells

机译：多种信号通路有助于凝血酶诱导的血管平滑肌细胞分泌表型。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors/PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.
机译：我们试图通过确定参与趋化因子产生的信号分子来研究血管平滑肌细胞（VSMC）表型改变的分子机制。用凝血酶处理人主动脉平滑肌细胞（HAoSMCs）不仅导致（C-C基序）配体11（CCL11）基因的转录升高，而且导致CCL11蛋白的分泌增强。 HAoSMC与蛋白激酶C的抑制剂GF109230X或Raf-1激酶的抑制剂GW5074共同处理，可抑制ERK1 / 2磷酸化，并在凝血酶诱导的转录和蛋白水平上显着减弱CCL11的表达。在存在百日咳毒素（PTX）（一种Gi蛋白偶联受体的抑制剂）或LY294002（一种PI3K抑制剂）的情况下，凝血酶诱导的Akt磷酸化和CCL11表达均减弱。另外，凝血酶诱导的CCL11的产生通过药理学上抑制ERK1 / 2磷酸化的Akt或MEK大大减弱。这些结果表明，凝血酶可能通过HAoSMCs中的PKC / Raf-1 / ERK1 / 2和PTX敏感蛋白酶激活的受体/ PI3K / Akt途径促进CCL11的表达。我们建议多个信号通路参与VSMCs分泌表型的变化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号