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学科主题: 临床医学
题名:
Transactivated EGFR mediates alpha(1)-AR-induced STAT3 activation and cardiac hypertrophy
作者: Li, Yan; Zhang, Hui; Liao, Wenqiang; Song, Yao; Ma, Xiaowei; Chen, Chao; Lu, Zhizhen; Li, Zijian; Zhang, Youyi1
关键词: alpha(1)-adrenergic receptor ; signal transducers and activators of transcription 3 ; epidermal growth factor receptor ; transactivation
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
发表日期: 2011-11-01
DOI: 10.1152/ajpheart.00338.2011
卷: 301, 期:5, 页:H1941-H1951
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Physiology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Physiology
关键词[WOS]: GROWTH-FACTOR-RECEPTOR ; VASCULAR SMOOTH-MUSCLE ; II TYPE-1 RECEPTOR ; ANGIOTENSIN-II ; CARDIOMYOCYTE HYPERTROPHY ; MYOCARDIAL-INFARCTION ; SIGNAL TRANSDUCER ; HEART-FAILURE ; G-PROTEIN ; PATHWAY
英文摘要:

Li Y, Zhang H, Liao W, Song Y, Ma X, Chen C, Lu Z, Li Z, Zhang Y. Transactivated EGFR mediates alpha(1)-AR-induced STAT3 activation and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 301: H1941-H1951, 2011. First published August 19, 2011; doi:10.1152/ajpheart.00338.2011.-Li Y, Zhang H, Liao W, Song Y, Ma X, Chen C, Lu Z, Li Z, Zhang Y. alpha(1)-Adrenergic receptor (alpha(1)-AR) is a crucial mediator of cardiac hypertrophy. Although numerous intracellular pathways have been implicated in alpha(1)-AR-induced hypertrophy, its precise mechanism remains elusive. We aimed to determine whether alpha(1)-AR induces cardiac hypertrophy through a novel signaling pathway-alpha(1)-AR/epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (STAT3). The activation of STAT3 by alpha(1)-AR was first demonstrated by tyrosine phosphorylation, nuclear translocation, DNA binding, and transcriptional activity in neonatal Sprague-Dawley rat cardiomyocytes. Activated STAT3 showed an essential role in alpha(1)-AR-induced cardiomyocyte hypertrophic growth, as assessed by treatment with STAT3 inhibitory peptide and lentivirus-STAT3 small interfering RNA. The results were further confirmed by in vivo experiments involving intraperitoneal injection of the STAT3 inhibitor WP1066 significantly inhibiting phenylephrine-infusion-induced heart hypertrophy in male C57BL/6 mice. Furthermore, the alpha(1)-AR-activated STAT3 was associated with transactivation of EGFR because inhibition of EGFR with the selective inhibitor AG1478 prevented alpha(1)-AR-induced STAT3 tyrosine phosphorylation and its transcriptional activity, as well as cardiac hypertrophy. In summary, these results suggest that alpha(1)-AR induces the activation of STAT3, mainly through transactivation of EGFR, which plays an important role in alpha(1)-AR-induced cardiac hypertrophy.

语种: 英语
所属项目编号: 2011CB503903 ; 309101039020 ; 81030001 ; 81070078 ; 7102158
项目资助者: National Key Basic Research Program of the People&prime ; s Republic of China ; Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation
WOS记录号: WOS:000296716900022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59486
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Key Lab Cardiovasc Mol Biol & Regulatory Peptide, Inst Vasc Med,Minist Hlth, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China

Recommended Citation:
Li, Yan,Zhang, Hui,Liao, Wenqiang,et al. Transactivated EGFR mediates alpha(1)-AR-induced STAT3 activation and cardiac hypertrophy[J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,2011,301(5):H1941-H1951.
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