生理性周期性张应变通过激活AMPK磷酸化抑制血管平滑肌细胞迁移
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上海交通大学

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Physiological Cyclic Stretch Inhibits Vascular Smooth Muscle Cell Migration via Activating AMPK Phosphorylation
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    摘要:

    目的 探讨细胞能量代谢的关键调节因子 AMP激活的蛋白激酶(AMPK) 在血管平滑肌细胞(vascular smooth muscle cells, VSMCs)响应生理性周期性张应变力学刺激后,对VSMCs迁移的影响。方法 采用 Flexcell 体外细胞张应变加载系统,对大鼠原代培养的 VSMCs 施加10% 幅度、1.25 Hz 频率的周期性张应变,模拟 VSMCs 在体内的生理性力学环境;以未加载周期性张应变的静态细胞为对照组,Western blotting 检测 VSMCs的 p-AMPK蛋白表达;划痕实验检测 VSMCs 迁移功能。结果 与静态组的细胞相比,生理性周期性张应变加载 24 h 后显著减少了划痕愈合面积,提示生理性周期性张应变抑制VSMCs 迁移;生理性周期性张应变加载 3 h 后,VSMCs 的 p-AMPK 蛋白表达显著升高,而加载 24 h 后 p-AMPK 的蛋白表达显著降低。在生理性周期性张应变加载条件下,孵育 AMPK 抑制剂可以在张应变加载 3 h 后显著降低 p-AMPK 的蛋白表达,而在张应变加载 24 h 后显著促进 VSMCs 迁移;在静态条件下孵育 AMPK 激活剂 AICAR 3 h 后显著诱导了 p-AMPK 的蛋白表达,孵育 24 h 后显著抑制了 VSMCs 迁移;提示p-AMPK的蛋白表达参与调控VSMCs 迁移。结论 生理性周期性张应变能通过激活 p-AMPK 的蛋白表达进而抑制 VSMCs 迁移,提示生理性周期性张应变调控 VSMCs 迁移对维持血管稳态具有重要意义。

    Abstract:

    Objective The aim of the current study is to explore the role of AMPK, a key regulator of cellular energy metabolism, in vascular smooth muscle cell (VSMC) migration in response to physiological cyclic stretch. Methods The Flexcell-5000T mechanical loading system was applied with a physiological cyclic stretch of 10% amplitude and 1.25 Hz frequency to primary rat VSMCs, to simulate the mechanical stimulation of VSMCs in vivo; The protein expression of p-AMPK in VSMCs was detected by Western blotting; VSMC migration was detected by wound healing test. Results Compared with the static group, physiological cyclic stretch loading for 24 h significantly decreased the area of wound healing, suggesting that physiological cyclic stretch inhibited VSMC migration. The protein expression of p-AMPK in VSMCs was increased significantly after physiological cyclic stretch loading for 3 h, and was decreased significantly after 24 h. Under physiological cyclic stretch loading conditions, incubating AMPK inhibitor can significantly reduce the protein expression of p-AMPK after 3 h, and promote VSMC migration after 24 h; incubating AMPK activator AICAR under static conditions significantly increased the protein expression of p-AMPK after 3 h, and weakened VSMC migration after 24 h. Conclusions Physiological cyclic stretch inhibits VSMC migration by increasing the protein expression of p-AMPK, suggesting that the VSMC migration regulated by physiological cyclic stretch is of great significance for maintaining vascular homeostasis.

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  • 收稿日期:2021-04-27
  • 最后修改日期:2021-05-18
  • 录用日期:2021-05-20
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