IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling

Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xinliang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan and Hongliang Li ()
Additional contact information
Ding-Sheng Jiang: Renmin Hospital of Wuhan University
Xiang Wei: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xiao-Fei Zhang: College of Life Sciences, Wuhan University
Yu Liu: Renmin Hospital of Wuhan University
Yan Zhang: Renmin Hospital of Wuhan University
Ke Chen: College of Life Sciences, Wuhan University
Lu Gao: Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Heng Zhou: Renmin Hospital of Wuhan University
Xue-Hai Zhu: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Peter P. Liu: University of Ottawa Heart Institute
Wayne Bond Lau: Thomas Jefferson University
Xinliang Ma: Thomas Jefferson University
Yunzeng Zou: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University
Xiao-Dong Zhang: College of Life Sciences, Wuhan University
Guo-Chang Fan: University of Cincinnati
Hongliang Li: Renmin Hospital of Wuhan University

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract 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.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4303 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4303

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4303

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().