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学科主题: 临床医学
题名:
Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*
作者: Xu, Xin-ye; Nie, Ying; Wang, Fang-fang; Bai, Yan; Lv, Zhi-zhen; Zhang, You-yi; Li, Zi-jian1; Gao, Wei
关键词: Cardiac Hypertrophy ; Cell Signaling ; Epidermal Growth Factor Receptor (EGFR) ; Growth Factors ; Hypertension ; Growth Differentiation Factor 15 ; Norepinephrine ; Transactivation
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2014-04-04
DOI: 10.1074/jbc.M113.516278
卷: 289, 期:14, 页:10084-10094
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: CHRONIC HEART-FAILURE ; SYMPATHETIC-NERVOUS-SYSTEM ; FACTOR-BETA SUPERFAMILY ; ACUTE CORONARY SYNDROME ; MOLECULAR-MECHANISMS ; ADULT CARDIOMYOCYTES ; EUROPEAN-SOCIETY ; DISEASE SEVERITY ; TASK-FORCE ; HYPERTENSION
英文摘要:

Background: The effect of GDF-15 on the regulation of cardiac remodeling is poorly understood. Results: GDF-15 inhibits norepinephrine induced EGF receptor transactivation and associated hypertrophy and positively associates with myocardial hypertrophy of hypertension patients. Conclusion: GDF-15 blocks norepinephrine-induced myocardial hypertrophy via a novel pathway involving inhibition of EGF receptor transactivation. Significance: We indicate a negative feedback mechanism of GDF-15 in regulating catecholamine-induced cardiac remodeling.

Accumulating evidence suggests that growth differentiation factor 15 (GDF-15) is associated with the severity and prognosis of various cardiovascular diseases. However, the effect of GDF-15 on the regulation of cardiac remodeling is still poorly understood. In this present study, we demonstrate that GDF-15 blocks norepinephrine (NE)-induced myocardial hypertrophy through a novel pathway involving inhibition of EGFR transactivation. Both in vivo and in vitro assay indicate that NE was able to stimulate the synthesis of GDF-15. The up-regulation of GDF-15 feedback inhibits NE-induced myocardial hypertrophy, including quantitation of [H-3]leucine incorporation, protein/DNA ratio, cell surface area, and ANP mRNA level. Further research shows that GDF-15 could inhibit the phosphorylation of EGF receptor and downstream kinases (AKT and ERK1/2) induced by NE. Clinical research also shows that serum GDF-15 levels in hypertensive patients were significant higher than in healthy volunteers and were positively correlated with the thickness of the posterior wall of the left ventricle, interventricular septum, and left ventricular mass, as well as the serum level of norepinephrine. In conclusion, NE induces myocardial hypertrophy and up-regulates GDF-15, and this up-regulation of GDF-15 negatively regulates NE-induced myocardial hypertrophy by inhibiting EGF receptor transactivation following NE stimulation.

语种: 英语
所属项目编号: PUCRP-004 ; 30910103902 ; 81270157 ; 81070078 ; 81121061 ; 2011CB503903 ; 7102158
项目资助者: Key Construction Program of the National 985 Project ; National Natural Science Foundation of China ; 973 Program of the Major State Basic Research Development Program of China ; Beijing Municipal Natural Science Foundation
WOS记录号: WOS:000333807000055
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57731
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Dept Cardiol, Hosp 3, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Minist Hlth, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
3.Beijing Key Lab Cardiovasic Receptors Res, Beijing 100191, Peoples R China

Recommended Citation:
Xu, Xin-ye,Nie, Ying,Wang, Fang-fang,et al. Growth Differentiation Factor (GDF)-15 Blocks Norepinephrineinduced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation*[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(14):10084-10094.
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