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Mesoderm/mesenchyme homeobox gene l promotes vascular smooth muscle cell phenotypic modulation and vascular remodeling

机译:Mesoderm / Mesenchyme Homeobox Gene L促进血管平滑肌细胞表型调节和血管重塑

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摘要

Abstract Aims To investigate the role of mesoderm/mesenchyme homeobox gene l (Meox1) in vascular smooth muscle cells (SMCs) phenotypic modulation during vascular remodeling. Methods and results By using immunostaining, Western blot, and histological analyses, we found that Meox1 was up-regulated in PDGF-BB-treated SMCs in vitro and balloon injury-induced arterial SMCs in vivo. Meox1 knockdown by shRNA restored the expression of contractile SMCs phenotype markers including smooth muscle α-actin (α-SMA) and calponin. In contrast, overexpression of Moex1 inhibited α-SMA and calponin expressions while inducing the expressions of synthetic SMCs phenotype markers such as matrix gla protein, osteopontin, and proliferating cell nuclear antigen. Mechanistically, Meox1 mediated the SMCs phenotypic modulation through FAK-ERK1/2 signaling, which appears to induce autophagy in SMCs. In vivo, knockdown of Meox1 attenuated injury-induced neointima formation and promoted SMCs contractile proteins expressions. Meox1 knockdown also reduced the number of proliferating SMCs, suggesting that Meox1 was important for SMCs proliferation in vivo. Moreover, knockdown of Meox1 attenuated ERK1/2 signaling and autophagy markers expressions, suggesting that Meox1 may promote SMCs phenotypic modulation via ERK1/2 signaling-autophagy in vivo. Conclusion Our data indicated that Meox1 promotes SMCs phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade. Thus, targeting Meox1 may be an attractive approach for treating proliferating vascular diseases.
机译:摘要旨在探讨Mesoderm / Mesenchyme Homeobox Gene L(MEOX1)在血管改造过程中血管平滑肌细胞(SMC)表型调节的作用。通过使用免疫染色,Western印迹和组织学分析的方法和结果,我们发现MEOX1在体外的体外和球囊损伤诱导的动脉SMC中对PDGF-BB处理的SMC上调。 Meox1通过ShRNA敲低恢复了收缩SMC表型标志物的表达,包括平滑肌α-肌动蛋白(α-SMA)和CALPONIN。相反,MoEx1的过表达抑制了α-SMA和CALPONIN表达,同时诱导合成SMC表型标志物如基质GLA蛋白,骨膨胀型蛋白和增殖细胞核抗原的表达。机械地,Meox1通过Fak-ERK1 / 2信号介导SMC表型调节,这似乎在SMC中诱导自噬。在体内,Meox1减弱损伤诱导的新琼蛋白形成和促进SMCS收缩蛋白表达的敲低。 Meox1敲低也降低了增殖SMC的数量,表明MEOX1对于体内SMC增殖非常重要。此外,Meox1减弱的ERK1 / 2信号传导和自噬标志物表达的敲低,表明MEOX1可以通过体内通过ERK1 / 2信号自噬促进SMC表型调节。结论我们的数据表明,Meox1通过调节FAK-ERK1 / 2自噬信号级联来促进SMCS表型调节和损伤诱导的血管重塑。因此,靶向MEOX1可以是治疗增殖血管疾病的有吸引力的方法。

著录项

  • 来源
    《International Journal of Cardiology》 |2018年第2018期|共8页
  • 作者单位

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Department of Nuclear Medicine Renmin Hospital Hubei University of Medicine;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

    Department of Physiology &

    Pharmacology The University of Georgia;

    Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 心脏、血管(循环系)疾病;
  • 关键词

    Mesoderm/mesenchyme homeobox gene l; Vascular smooth muscle cells; Phenotypic modulation; Vascular remodeling;

    机译:Mesoderm / Mesenchyme Homeobox基因L;血管平滑肌细胞;表型调节;血管改造;

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