共 33 条
Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload
被引:17
作者:

Li, Wei-ming
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机构:
Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Zhao, Yi-fan
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Zhu, Guo-fu
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Peng, Wen-hui
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Zhu, Meng-yun
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Yu, Xue-jing
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Chen, Wei
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Xu, Da-chun
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Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

Xu, Ya-wei
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机构:
Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China
机构:
[1] Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China
基金:
中国国家自然科学基金;
关键词:
cardiac hypertrophy;
dual specific phosphatase 12;
c-Jun N-terminal kinase (JNK);
signalling pathway;
SP600125;
N-TERMINAL KINASE;
HEART-FAILURE;
ACTIVATION;
REGULATORS;
CARDIOMYOPATHY;
IDENTIFICATION;
APOPTOSIS;
REVEALS;
BINDING;
ERK1/2;
D O I:
10.1042/CS20160664
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.
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收藏
页码:141 / 154
页数:14
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机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Zhang, Xiao-Jing
论文数: 0 引用数: 0
h-index: 0
机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Zhao, Yi-Chao
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h-index: 0
机构:
Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Dept Cardiol, Shanghai 200127, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Deng, Ke-Qiong
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h-index: 0
机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Jiang, Xi
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h-index: 0
机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Wang, Pi-Xiao
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h-index: 0
机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Huang, Zan
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h-index: 0
机构:
Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

Li, Hongliang
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h-index: 0
机构:
Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China
Wuhan Univ, Anim Expt Ctr, Anim Biosafety Level Lab 3, Wuhan 430060, Peoples R China
Wuhan Univ, Med Res Inst, Sch Med, Wuhan 430071, Peoples R China Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China