NR6A1 couples with cAMP response element binding protein and regulates vascular smooth muscle cell migration

被引：16

作者：

Wang, Yinfang ^{[1
]}

Zhang, Yahui ^{[3
]}

Dai, Xiuqin ^{[1
]}

Liu, Zongjun ^{[2
]}

Yin, Peihao ^{[1
]}

Wang, Nanping ^{[4
]}

Zhang, Peng ^{[1
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Cent Lab, Shanghai 200062, Peoples R China

[2] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Cardiovasc Med, Shanghai 200062, Peoples R China

[3] Hubei Univ Med, Dept Pathophysiol, Wuhan, Hubei, Peoples R China

[4] Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2015年 / 69卷

基金：

中国国家自然科学基金;

关键词：

NR6A1; Smooth muscle cell; Migration; CREB; SPP1; NUCLEAR RECEPTOR GCNF; ORPHAN RECEPTOR; IL-6; EXPRESSION; ACTIN; OSTEOPONTIN; PROLIFERATION; REPRESSION; CREB; ALPHA; ATHEROSCLEROSIS;

D O I：

10.1016/j.biocel.2015.10.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vascular smooth muscle cell (VSMC) migration is implicated in atherosclerosis and restenosis. Nuclear receptor subfamily 6, group A, member 1 (NR6A1) is involved in regulating embryonic stem cell differentiation, reproduction, neuronal differentiation. Functional cooperation between cAMP response element modulator tau (CREMtau) and NR6A1 can direct gene expression in cells. cAMP response element binding protein (CREB) plays a key role in VSMC migration. In this study, we sought to determine whether CREB involved in NR6A1-modulated VSMC migration. VSMCs treated with platelet-derived growth factor-BB (PDGF-BB) displayed reduced mRNA and protein levels of NR6A1. Adenovirus-mediated expression of NR6A1 (Ad-NR6A1) could inhibit PDGF-BB- and serum-induced VSMC migration. The mRNA and protein expressions of secreted phosphoprotein 1 (SPP1) were down-regulated by NR6A1 overexpression. SPP1 promoter reporter activity was repressed by NR6A1. NR6A1 was found to physically couple with nuclear actin and the large subunit of RNA polymerase II. Furthermore, we showed that CREB interacted with NR6A1 in VSMCs. NR6A1 overexpression repressed CAMP response element (CRE) activity. ChIP assay revealed that NR6A1 bind to SPP1 promoter. Luciferase reporter assay showed that NR6A1 regulated SPP1 promoter activity via a putative CRE site. Adenovirus mediated local NR6A1 gene transfer attenuated stenosis after balloon-induced arterial injury in Sprague-Dawley rats. Taken together, this study provided experimental evidence that NR6A1 modulated SPP1 expression via its binding with CREB protein in VSMCs. We also revealed a NR6A1-CREB-SPP1 axis that serves as a regulatory mechanism for atherosclerosis and restenosis. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：225 / 232

页数：8

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