Abstract：
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. 17β-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. ERα agonist PPT, but not ERβ 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 ERα to ERK1/2 pathway, which maybe helpful to understand estrogen\'s anti-atherogenic effect in VSMCs.
摘要：
纹状体,雌激素受体（ER）相互作用蛋白，雌激素在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VSMC中的作用尚不清楚.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.10nM的17β-雌二醇（E2）在很大程度上抑制了VSMC的迁移，通过纹状体蛋白表达的沉默而逆转。E2以剂量和时间依赖性方式增加纹状体蛋白表达。ERα激动剂PPT，但不是ERβ激动剂DPN，模仿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ICI182,780或丝裂原活化蛋白激酶抑制剂PD98059阻断，但磷脂酰肌醇-3激酶抑制剂wortmannin或Src抑制剂PP2未阻断，表明E2通过细胞外信号调节激酶1/2（ERK1/2）增加纹状体蛋白表达。E2以时间依赖性方式导致ERK1/2的磷酸化。ERK1/2的沉默在很大程度上消除了E2增强的纹状体蛋白表达。最后,E2对VSMC迁移的抑制作用被ICI182,780或PD98059逆转。一起来看,我们的结果表明，E2抑制VSMC迁移通过增加纹状体蛋白表达通过ERα到ERK1/2途径，这可能有助于了解雌激素在VSMC中的抗动脉粥样硬化作用。
