Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro

Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro
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DOI:
10.1016/j.yexcr.2009.10.025
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发表时间:
2010-04-01
影响因子:
3.7
通讯作者:
Sobue, Kenji
Sobue, Kenji
中科院分区:
医学3区
文献类型:
--
作者:
Oikawa, Hiroki;Hayashi, Ken'ichiro;Sobue, Kenji

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巢蛋白是一种在神经和间充质干细胞中表达的中间丝蛋白。在此,我们研究巢蛋白在血管平滑肌细胞(VSMCs)在体内和体外的表达。在发育中的动脉中,发现内侧VSMC表达巢蛋白;其表达在胚胎中突出,但在出生后(3-6周)以区域依赖性方式下调;其表达在成人中被废除。因此,巢蛋白的表达是特异性的发展VSMCs。在原代培养的VMSC中,巢蛋白表达由血清诱导,但不依赖于细胞周期进程。信号分析表明,血清诱导的巢蛋白表达依赖于细胞外信号调节激酶(ERK)和蛋白激酶B(PKB)(Akt)途径,通过血小板衍生生长因子(PDGF)和表皮生长因子(EGF)受体。Nestin的表达与Sp1和Sp3的上调和激活密切相关。在主要的血清生长因子和细胞因子中,PDGF-BB是巢蛋白表达的最有效的诱导剂。巢蛋白在球囊损伤后经历血管重塑的动脉中也上调。它的表达是特别强的细胞内衬的管腔的新生内膜,表明巢蛋白表达和血管重塑的进展之间可能存在相关性。(C)2009 Elsevier Inc. All rights reserved.
Nestin is an intermediate filament protein expressed in neural and mesenchymal stem cells. Here, we investigated the expression of nestin in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In the developing arteries, medial VSMCs were found to express nestin; its expression was prominent in embryos but was down-regulated after birth (3-6 weeks) in a region-dependent manner; its expression was abolished in the adult. Thus, the expression of nestin is specific to developing VSMCs. In primary VMSC cultures, nestin expression was induced by serum, but was independent of cell-cycle progression. Signaling analyses revealed that the serum-induced nestin expression depended on the extracellular signal-regulated kinase (ERK) and protein kinase B (PKB)(Akt) pathways, via the platelet derived growth factor (PDGF) and epidermal growth factor (EGF) receptors. Nestin expression was closely related to the up-regulation and activation of Sp1 and Sp3. Among major serum growth factors and cytokines, PDGF-BB was the most potent inducer of nestin expression. Nestin was also up-regulated in arteries undergoing vascular remodeling following balloon injury. Its expression was particularly strong in the cells lining the lumen of the neointima, suggesting a possible correlation between nestin expression and the progression of vascular remodeling. (C) 2009 Elsevier Inc. All rights reserved.