17β-Estradiol inhibits vascular smooth muscle cell migration via up-regulation of striatin protein
17β-Estradiol inhibits vascular smooth muscle cell migration via up-regulation of striatin protein
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17β-雌二醇通过上调条纹蛋白抑制血管平滑肌细胞迁移
DOI：
10.3109/09513590.2015.1021325
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发表时间：
2015-01-01
影响因子：
2
通讯作者：
Fu, Xiaodong
中科院分区：
文献类型：
--
作者：
Zheng, Shuhui;Chen, Xi;Fu, Xiaodong
Striatin是一种雌激素受体（ER）相互作用蛋白，在雌激素对血管内皮细胞的非基因组作用中起重要作用。然而，纹状体蛋白在血管平滑肌细胞中的作用尚不清楚。在这里，我们研究了纹状体蛋白在雌激素调节的VSMCs迁移中的作用。10 nM的17 β-雌二醇（E2）在很大程度上抑制了VSMCs的迁移，这通过抑制纹状体蛋白表达而逆转。E2以剂量和时间依赖性方式增加纹状体蛋白表达。ER α激动剂PPT，而不是ER β激动剂DPN，模拟E2的调节作用。E2对纹状体蛋白表达的调节作用被纯ER拮抗剂ICI 182，780或丝裂原活化蛋白激酶抑制剂PD 98059阻断，但不被磷脂酰肌醇-3激酶抑制剂wortmannin或Src抑制剂PP 2阻断，表明E2通过细胞外信号调节激酶1/2（ERK 1/2）增加纹状体蛋白表达。E2以时间依赖性方式导致ERK 1/2磷酸化。ERK 1/2的沉默在很大程度上消除了E2增强的纹状体蛋白表达。E2对VSMC迁移的抑制作用可被ICI 182，780或PD 98059逆转。综上所述，我们的结果表明，E2抑制VSMC迁移通过增加纹状体蛋白的表达，通过ERa到ERK 1/2途径，这可能有助于了解雌激素的抗动脉粥样硬化作用在VSMC。
Striatin, an estrogen receptor (ER)-interacting protein, plays an important role in estrogen's nongenomic actions in vascular endothelial cells. However, the role of striatin in VSMCs is unknown. Here, we investigated the role of striatin in estrogen-regulated VSMCs migration. 17 beta-Estradiol (E2) at 10 nM largely inhibited VSMCs migration, which was reversed by the silencing of striatin expression. E2 increased striatin protein expression in a dose- and time-dependent manner. ER alpha agonist PPT, but not ER beta agonist DPN, mimicked the regulatory effect of E2. The regulatory effect of E2 on striatin protein expression was blocked by the pure ER antagonist ICI 182,780 or the mitogen-activated protein kinase inhibitor PD98059, but not by the phosphatidylinositol-3 kinase inhibitor wortmannin or Src inhibitor PP2, suggesting that E2 increased striatin protein expression via extracellular-signal regulated kinase 1/2 (ERK1/2). E2 resulted in phosphorylation of ERK1/2 in a time-dependent manner. The silencing of ERK1/2 largely abolished E2-enhanced striatin expression. Finally, the inhibitory effect of E2 on VSMC migration was reversed by ICI 182,780 or PD98059. Taken together, our results indicate that E2 inhibits VSMC migration by increasing striatin expression via ERa to ERK1/2 pathway, which maybe helpful to understand estrogen's anti-atherogenic effect in VSMCs.