HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPβ Axis

被引：7

作者：

Bei, Yihua ^{[1
,2
]}

Zhu, Yujiao ^{[1
,2
]}

Wei, Meng ^{[1
,2
]}

Yin, Mingming ^{[1
,2
]}

Li, Lin ^{[1
,2
]}

Chen, Chen ^{[1
,2
]}

Huang, Zhenzhen ^{[1
,2
]}

Liang, Xuchun ^{[1
,2
]}

Gao, Juan ^{[1
,2
]}

Yao, Jianhua ^{[3
,4
]}

van der Kraak, Petra H. ^{[5
]}

Vink, Aryan ^{[5
]}

Lei, Zhiyong ^{[6
,7
]}

Dai, Yuxiang ^{[8
]}

Chen, Huihua ^{[9
]}

Liang, Yueyang ^{[9
]}

Sluijter, Joost P. G. ^{[6
,10
]}

Xiao, Junjie ^{[1
,2
]}

机构：

[1] Shanghai Univ, Inst Geriatr, Affiliated Nantong Hosp, Peoples Hosp Nantong 6,Sch Med, Nantong 226011, Peoples R China

[2] Shanghai Univ, Cardiac Regenerat & Ageing Lab, Inst Cardiovasc Sci, Shanghai Engn Res Ctr Organ Repair,Sch Life Sci, Shanghai 200444, Peoples R China

[3] Tongji Univ, Shanghai Peoples Hosp 10, Dept Cardiol, Sch Med, Shanghai 200072, Peoples R China

[4] Shigatse Peoples Hosp, Dept Cardiol, Tibet 857000, Peoples R China

[5] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands

[6] Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands

[7] Univ Utrecht, Univ Med Ctr Utrecht, Div Lab, Cent Diag Lab Res, NL-3584 CX Utrecht, Netherlands

[8] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai 200032, Peoples R China

[9] Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China

[10] Univ Med Ctr Utrecht, UMC Utrecht Regenerat Med Ctr, NL-3508 GA Utrecht, Netherlands

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 18期

基金：

欧洲研究理事会; 中国国家自然科学基金; 上海市自然科学基金;

关键词：

C/EBP beta; cardiomyocytes; CREB; HIPK1; pathological hypertrophy; ACTIVATION; GROWTH; GENE; LOCALIZATION; REGULATOR; PATHWAY; ROLES;

D O I：

10.1002/advs.202300585

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Inhibition of pathological cardiac hypertrophy is recognized as an important therapeutic strategy for heart failure, although effective targets are still lacking in clinical practice. Homeodomain interacting protein kinase 1 (HIPK1) is a conserved serine/threonine kinase that can respond to different stress signals, however, whether and how HIPK1 regulates myocardial function is not reported. Here, it is observed that HIPK1 is increased during pathological cardiac hypertrophy. Both genetic ablation and gene therapy targeting HIPK1 are protective against pathological hypertrophy and heart failure in vivo. Hypertrophic stress-induced HIPK1 is present in the nucleus of cardiomyocytes, while HIPK1 inhibition prevents phenylephrine-induced cardiomyocyte hypertrophy through inhibiting cAMP-response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer-binding protein.. (C/EBP ss)-mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy. In conclusion, HIPK1 inhibition may serve as a promising novel therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.

引用

页数：15

共 45 条

[11] Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis [J].