title: 17β-Estradiol inhibits vascular smooth muscle cell migration via up-regulation of striatin protein.
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.
authors.affiliation: a Research Center of Translational Medicine, the First Affiliated Hospital, Sun Yat-Sen University , Guangzhou , Guangdong Province , China .
authors.forename: Shuhui
authors.initials: S
authors.lastname: Zheng
authors.affiliation: b Department of Rehabilitation Medicine , the Third Affiliated Hospital, Sun Yat-sen University , Guangzhou , Guangdong Province , China .
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: c Department of Endocrinology , the First Affiliated Hospital, Sun Yat-Sen University , Guangzhou , Guangdong Province , China .
authors.forename: Shubin
authors.initials: S
authors.lastname: Hong
authors.affiliation: a Research Center of Translational Medicine, the First Affiliated Hospital, Sun Yat-Sen University , Guangzhou , Guangdong Province , China .
authors.forename: Lingli
authors.initials: L
authors.lastname: Long
authors.affiliation: a Research Center of Translational Medicine, the First Affiliated Hospital, Sun Yat-Sen University , Guangzhou , Guangdong Province , China .
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Xu
authors.affiliation: d Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development , University of Pisa , Pisa , Italy , and.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.affiliation: e School of Basic Sciences, Guangzhou Medical University , Guangzhou , Guangdong Province , China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002148:Calmodulin-Binding Proteins; D065171:Estrogen Receptor Antagonists; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C114095:Strn protein, rat; D000077267:Fulvestrant; D004958:Estradiol
keywords: 17β-Estradiol; extracellular-signal regulated kinase ½; migration; striatin; vascular smooth muscle cell