SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch
SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch
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SIRT1和FOXO介导循环拉伸下血管平滑肌细胞的收缩分化
DOI：
10.1159/000438544
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Jiang, Zong-Lai
中科院分区：
文献类型：
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作者：
Huang, Kai;Yan, Zhi-Qiang;Jiang, Zong-Lai
背景/目标：生理性机械牵张有助于维持血管平滑肌细胞（VSMCs）的静态收缩分化，但其机制尚不清楚。在这里，我们研究了SIRT 1在VSMC分化中对机械周期性拉伸的反应。方法：采用FX-4000 T体外培养系统，对大鼠VSMCs进行10%-1.25Hz的周期性牵张。数据表明，与静态对照相比，在经历周期性拉伸的VSMC中，收缩标记物（包括α-肌动蛋白、钙调蛋白和SM 22 α）的表达显著增强。牵张可使SIRT 1和FOXO 3a的表达增加，FOXO 4的表达减少。通过siRNA转染减少SIRT 1减弱了牵张诱导的收缩性VSMC标志物和FOXO 3a的表达。此外，增加SIRT 1的激活剂白藜芦醇或转染质粒诱导过表达增加FOXO 3a和收缩标志物的表达，并减少FOXO 4在VSMC中的表达。在SIRT 1（+/-）敲除小鼠的VSMC中观察到类似的趋势。FOXO 3a的过表达促进了VSMC收缩标志物的表达，而FOXO 4的过表达则表现出相反的作用。结论：我们的研究结果表明，生理周期性牵张通过SIRT 1/FOXO通路促进VSMCs的收缩分化，从而有助于维持血管稳态。版权所有（C）2015 S. Karger AG，巴塞尔
Background/Aims: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. Methods and Results: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including alpha-actin, calponin and SM22 alpha, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. Conclusion: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis. Copyright (C) 2015 S. Karger AG, Basel