IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling

被引：138

作者：

Jiang, Ding-Sheng ^{[1
,2
]}

Wei, Xiang ^{[3
]}

Zhang, Xiao-Fei ^{[4
]}

Liu, Yu ^{[1
,2
]}

Zhang, Yan ^{[1
,2
]}

Chen, Ke ^{[4
]}

Gao, Lu ^{[5
]}

Zhou, Heng ^{[1
,2
]}

Zhu, Xue-Hai ^{[3
]}

Liu, Peter P. ^{[6
]}

Lau, Wayne Bond ^{[7
]}

Ma, Xinliang ^{[7
]}

Zou, Yunzeng ^{[8
]}

Zhang, Xiao-Dong ^{[4
]}

Fan, Guo-Chang ^{[9
]}

Li, Hongliang ^{[1
,2
]}

机构：

[1] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China

[2] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thorac & Cardiovasc Surg, Wuhan 430030, Peoples R China

[4] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

[5] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Cardiol,Inst Cardiovasc Dis, Wuhan 430030, Peoples R China

[6] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada

[7] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA

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

[9] Univ Cincinnati, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

中国国家自然科学基金;

关键词：

INTERFERON REGULATORY FACTOR-8; ACTIVATED T-CELLS; INTRAPHAGOSOMAL PATHOGENS; TRANSCRIPTION FACTORS; NUCLEAR FACTOR; HYPERTROPHY; PROTEIN; INDUCTION; TUMOR; EXPRESSION;

D O I：

10.1038/ncomms4303

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits the hypertrophic response. Inhibition of NFATc1 ameliorates the cardiac abnormalities in IRF8(-/-) mice after AB. In contrast, constitutive activation of NFATc1 nullifies the protective effects of IRF8 on cardiac hypertrophy in IRF8-overexpressing mice. Our results indicate that IRF8 is a potential therapeutic target in pathological cardiac hypertrophy.

引用

页数：14

共 46 条

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A multi-functional role of interferon regulatory factor-8 in solid tumor and myeloid cell biology [J].