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心肌素在周期性张应变调控血管平滑肌细胞表型转化中的作用
作者:
作者单位:

(1.湖南中医药大学药学院,湖南省长沙市410208;2.湖南中医药大学中西结合学院,湖南省长沙市410208)

作者简介:

潘敏熇,硕士研究生,研究方向为心血管药理,E-mail为1025080043@qq.com。通信作者郑熙隆,博士,教授,博士研究生导师,研究方向为心血管药理,E-mail为xilingzheng@qq.com。通信作者廖端芳,博士,教授,博士研究生导师,研究方向为心血管药理,E-mail为dfliao@hnucm.edu.cn。

基金项目:

国家自然科学基金项目(81773736)


Role of myocardin in the regulation of phenotypic transformation of vascular smooth muscle cell by cyclic stretch
Author:
Affiliation:

1.School of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, China;2.College of Chinese and Western Combination, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, China)

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    摘要:

    目的 探讨周期性张应变条件下诱导血管平滑肌细胞(VSMC)表型转换时,心肌素在其中可能的作用。方法 应用FX-5000T体外周期性张应变加载系统,分别对体外培养的VSMC施加频率为1.25 Hz、加载幅度为5%(正常张应变状态)、15%(高张应变状态)的周期性张应变力学刺激,加载时间为24 h。采用蛋白免疫印迹法和实时荧光定量PCR技术检测心肌素、肌肉萎缩相关基因1(atrogin-1)及相关收缩蛋白SMA、SM22的蛋白表达水平和mRNA水平；敲除atrogin-1后测心肌素及相关收缩蛋白SMA、SM22的变化；用蛋白酶体抑制剂MG132处理后测心肌素和atrogin-1的表达水平。结果 与5%正常张应变组比较,15%高张应变促进平滑肌细胞的去分化。15%高张应变下调心肌素和SMA、SM22蛋白水平；上调atrogin-1蛋白表达水平；下调心肌素和SMA、SM22的mRNA水平,上调atrogin-1 mRNA水平。应用siRNA特异性下调atrogin-1后,心肌素、SMA、SM22蛋白水平均上升。用1 μmol/L MG132处理细胞后,心肌素、SMA、SM22的蛋白水平上升,atrogin-1蛋白水平下降。结论 周期性高张应变可以通过调节血管平滑肌细胞中atrogin-1/心肌素轴来调控血管平滑肌表型转换,进而影响VSMC的分化增殖。

    Abstract:

    Aim To investigate the possible role of myocardin in the vascular remodeling of vascular smooth muscle cell (VSMC) induced by high cyclic tensile stress. Methods Using FX-5000T in vitro cyclic stretch loading system, the VSMC in vitro were stimulated by cyclic stretch with frequency of 1.25 Hz, loading amplitude of 5% (normal physiological state) and 15% (simulated hypertension state) for 24 hours; Western blot and real time RT-PCR were used to detect the protein expression level and mRNA level of myocardin, atrogin-1, SMA and SM22. The expression level of myocardin and atrogin-1 were measured after the treatment with proteasome inhibitor MG132. The alteration of myocardin, SMA and SM22 was measured after the knockdown of atrogin-1. Results Compared with 5% normal group, 15% cyclic stretch promoted the dedifferentiation of SMCs. Western blot showed that 15% of cyclic stretch decreased the protein le-vels of myocardin, SMA and SM22, and increased the protein expression level of atrogin-1. RT-PCR showed that the mRNA levels of myocardin, SMA and SM22 were down regulated, and the mRNA level of atrogin-1 was up regulated. The results showed that the protein levels of myocardin, SMA and SM22 increased after siRNA down-regulation of atrogin-1. The protein levels of myocardin, SMA and SM22 increased and the protein level of atrogin-1 decreased after treated with 1 μmol/L MG132. Conclusion High cyclic stretch can regulate phenotypic transformation of VSMC by regulating the expression of myocardin, an important transcription co-factor, thus affecting the differentiation and proliferation of VSMC.

    参考文献
    [1] Owens GK, Kumar MS, Wamhoff BR.Molecular regulation of vascular smooth muscle cell differentiation in development and disease.Physiol Rev, 4,4(3):767-801.
    [2] Wang G, Jacquet L, Karamariti E, et al.Origin and differentiation of vascular smooth muscle cell.J Physiol, 5,3(14):3013-3030.
    [3] Li S, Wang DZ, Wang Z, et al.The serum response factor coactivator myocardin is required for vascular smooth muscle development.Proc Natl Acad Sci USA, 3,0(16):9366-9370.
    [4] Zheng XL.Myocardin and smooth muscle differentiation.Arch Biochem Biophys, 4,3:48-56.
    [5] Kang SH, Lee HA, Kim M, et al.Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in cushing's syndrome.Am J Physiol Endocrinol Metab, 7,2(6):E495-E507.
    [6] Singh P, Li D, Gui Y, et al.Atrogin-1 increases smooth muscle contractility through myocardin degradation.J Cell Physiol, 7,2(4):806-817.
    [7] Chiu JJ, Chien S.Effects of disturbed flow on vascular endothelium:pathophysiological basis and clinical perspectives.Physiol Rev, 1,1(1):327-387.
    [8] Safar ME, Peronneau PA, Levenson JA, et al.Pulsed doppler:diameter, blood flow velocity and volumic flow of the brachial artery in sustained essential hypertension.Circulation, 1,3(2):393-400.
    [9] Tan X, Gao J, Shi Z, et al.MG132 induces expression of monocyte chemotactic protein-induced protein 1 in vascular smooth muscle cells.J Cell Physiol, 7,2(1): 122-128.
    [10] Xia XD, Zhou Z, Yu XH, et al.Myocardin:a novel player in atherosclerosis.Atherosclerosis, 7,7:266-278.
    [11] Wang D, Chang PS, Wang Z, et al.Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.Cell, 1,5(7):851-862.
    [12] Sun HJ, Ren XS, Xiong XQ, et al.NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension.Cell Death Dis, 7,8(10):e3074.
    [13] Gao F, Huang Y, Zhang L, et al.Involvement of estrogen receptor and GPER in bisphenol a induced proliferation of vascular smooth muscle cell.Toxicol In Vitro, 9,6:156-162.
    [14] Liu Y, Peng W, Qu K, et al.TET2:a novel epigenetic regulator and potential intervention target for atherosclerosis.DNA Cell Biol, 8,7(6):517-523.
    [15] Li H, Xiang Y, Fan LJ, et al.Myocardin inhibited the gap protein connexin 43 via promoted miR-206 to regulate vascular smooth muscle cell phenotypic switch.Gene, 7,6:22-30.
    [16] Lu QB, Wan MY, Wang PY, et al.Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NF-κB/mTOR/P70S6K signaling cascade.Redox Biol, 8,4:656-668.
    [17] Zhao J, Wu W, Zhang W, et al.Selective expression of TSPAN2 in vascular smooth muscle is independently regulated by TGF-β1/SMAD and myocardin/serum response factor.FASEB J, 7,1(6):2576-2591.
    [18] Tang RH, Zheng XL, Callis TE, et al.Myocardin inhibits cellular proliferation by inhibiting NF-kappaB(p65)-dependent cell cycle progression.Proc Natl Acad Sci USA, 8,5(9):3362-3367.
    [19] Campos LCG, Ribeiro-Silva JC, Menegon AS, et al.Cyclic stretch-induced Crp3 sensitizes vascular smooth muscle cell to apoptosis during vein arterialization remodeling.Clin Sci (Lond), 8,2(4):449-459.
    [20] Chien S.Mechanotransduction and endothelial cell homeo-stasis:the wisdom of the cell.Am J Physiol Heart Circ Physiol, 7,2(3):H1209-H1224.
    [21] Qi YX, Yao QP, Huang K, et al.Nuclear envelope proteins modulate proliferation of vascular smooth muscle cell during cyclic stretch application.Proc Natl Acad Sci USA, 6,3(19):5293-5298.
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潘敏熇,郑熙隆,廖端芳.心肌素在周期性张应变调控血管平滑肌细胞表型转化中的作用[J].中国动脉硬化杂志,2020,28(9):749~756.

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  • 收稿日期:2020-04-27
  • 最后修改日期:2020-06-04
  • 在线发布日期: 2020-10-28

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