IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Shear stress activation of nuclear receptor PXR in endothelial detoxification
Wang, Xiaohong1,2,3,4,5; Fang, Xi1,2; Zhou, Jing3,4,5; Chen, Zhen3,4,5; Zhao, Beilei1,2; Xiao, Lei6; Liu, Ao1,2; Li, Yi-Shuan J.3,4,5; Shyy, John Y. -J.3,4,5,6; Guan, Youfei1,2; Chien, Shu3,4,5; Wang, Nanping1,2,6
关键词hemodynamics endothelial homeostasis nuclear hormone receptor gene regulation
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013-08-06
DOI10.1073/pnas.1312065110
110期:32页:13174-13179
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]PREGNANE-X-RECEPTOR ; REGULATES DRUG-METABOLISM ; NITRIC-OXIDE SYNTHASE ; RESPONSE ELEMENT ; P-GLYCOPROTEIN ; CELL APOPTOSIS ; IN-VITRO ; EXPRESSION ; INDUCTION ; FLOW
英文摘要

Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-alpha and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics.

语种英语
WOS记录号WOS:000322771100074
项目编号30890041 ; 81220108005 ; 2010CB912500 ; HL108735-01A1
资助机构National Science Foundation of China ; Ministry of Science and Technology of China ; National Institutes of Health
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58978
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
2.Peking Univ, Minist Educ, Key Lab Mol Cardiol, Beijing 100191, Peoples R China
3.Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
4.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
5.Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA
6.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian 710061, Peoples R China
推荐引用方式
GB/T 7714
Wang, Xiaohong,Fang, Xi,Zhou, Jing,et al. Shear stress activation of nuclear receptor PXR in endothelial detoxification[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2013,110(32):13174-13179.
APA Wang, Xiaohong.,Fang, Xi.,Zhou, Jing.,Chen, Zhen.,Zhao, Beilei.,...&Wang, Nanping.(2013).Shear stress activation of nuclear receptor PXR in endothelial detoxification.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,110(32),13174-13179.
MLA Wang, Xiaohong,et al."Shear stress activation of nuclear receptor PXR in endothelial detoxification".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.32(2013):13174-13179.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
PNAS-2013-Wang-13174(1008KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Wang, Xiaohong]的文章
[Fang, Xi]的文章
[Zhou, Jing]的文章
百度学术
百度学术中相似的文章
[Wang, Xiaohong]的文章
[Fang, Xi]的文章
[Zhou, Jing]的文章
必应学术
必应学术中相似的文章
[Wang, Xiaohong]的文章
[Fang, Xi]的文章
[Zhou, Jing]的文章
相关权益政策
暂无数据
收藏/分享
文件名: PNAS-2013-Wang-13174-9.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。