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FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury
Jia, Shi1; Chen, Zhenzhen1; Li, Jing2; Chi, Yujing3,4; Wang, Jinyu1; Li, Sha1; Luo, Yanjin1; Geng, Bin1; Wang, Cheng1; Cui, Qinghua1; Guan, Youfei1; Yang, Jichun1
关键词FAM3A VSMCs Proliferation P2Y receptor EP2
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2014-09-01
DOI10.1016/j.yjmcc.2014.05.011
74页:173-182
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Cell Biology
研究领域[WOS]Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]PROSTAGLANDIN RECEPTOR EP2 ; PANCREATIC-DERIVED FACTOR ; P2 RECEPTORS ; SIGNALING PATHWAY ; EXTRACELLULAR ATP ; DOWN-REGULATION ; GENE FAMILY ; EXPRESSION ; NEURONS ; DISEASE
英文摘要

The biological function of FAM3A, the first member of family with sequence similarity 3 (FAM3) gene family, remains largely unknown. This study aimed to determine its role in the proliferation and migration of vascular smooth muscle cells (VSMCs). Immunohistochemical staining revealed that FAM3A protein is expressed in the tunica media of rodent arteries, and its expression is reduced with an increase in prostaglandin E receptor 2 (EP2) expression after injury. In vitro, FAM3A overexpression promotes proliferation and migration of VSMCs, whereas FAM3A silencing inhibits these processes. In vivo, FAM3A overexpression results in exaggerated neointima formation of rat carotid artery after balloon injury. FAM3A activates Akt in a PI3K-dependent manner. In contrast, FAM3A induces ERK1/2 activation independent of PI3K. FAM3A protein is subcellularly located in mitochondria, where it affects ATP production and release. Activation of EP2 represses FAM3A expression, leading to impaired ATP production and release in VSMCs. FAM3A-induced activation of Akt and ERK1/2 pathways, proliferation and migration of VSMCs are inhibited by P2 receptor antagonist suramin. Furthermore, inhibition or knockdown of P2Y1 receptor inihibits FAM3A-induced proliferation and migration of VSMCs. In conclusion, FAM3A promotes proliferation and migration of VSMCs via P2Y1 receptor-mediated activation of Akt and ERK1/2 pathways. In injured vessels, FAM3A was repressed by upregulated EP2 expression, leading to the attenuation of ATP-P2Y1 receptor signaling, which is beneficial for preventing excessive proliferation and migration of VSMCs. (C) 2014 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000340077900020
项目编号2012CB517504/2012CB517806 ; 81170791/81200625/81200626/81322011 ; 7122107
资助机构Ministry of Science and Technology of the People&prime ; s Republic of China ; Natural Science Foundation of China ; Beijing Natural Science Foundation
引用统计
被引频次:11[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/400002259/66694
专题北京大学第二临床医学院_消化科
北京大学基础医学院
北京大学第一临床医学院_医学影像科
北京大学第二临床医学院_中心实验室
作者单位1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci,Minist Educ, Dept Physiol & Pathophysiol,Key Lab Mol Cardiovas, Beijing 100191, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100044, Peoples R China
3.Peking Univ, Inst Clin Mol Biol, Beijing 100044, Peoples R China
4.Peking Univ, Cent Lab, Beijing 100044, Peoples R China
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GB/T 7714
Jia, Shi,Chen, Zhenzhen,Li, Jing,et al. FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2014,74:173-182.
APA Jia, Shi.,Chen, Zhenzhen.,Li, Jing.,Chi, Yujing.,Wang, Jinyu.,...&Yang, Jichun.(2014).FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,74,173-182.
MLA Jia, Shi,et al."FAM3A promotes vascular smooth muscle cell proliferation and migration and exacerbates neointima formation in rat artery after balloon injury".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 74(2014):173-182.
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