Document Type
Article
Publication Date
2-14-2014
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.
Recommended Citation
Jiang, Ding-Sheng; Wei, Xiang; Zhang, Xiao-Fei; Liu, Yu; Zhang, Yan; Chen, Ke; Gao, Lu; Zhou, Heng; Zhu, Xue-Hai; Liu, Peter P.; Lau, Wayne Bond; Ma, Xin-Liang; Zou, Yunzeng; Zhang, Xiao-Dong; Fan, Guo-Chang; and Li, Hongliang, "IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling." (2014). Department of Emergency Medicine Faculty Papers. Paper 150.
https://jdc.jefferson.edu/emfp/150
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
PubMed ID
24526256
Language
English
Comments
This article is the authors’ final published version in Nature Communications, Volume 5, February 2014, Article number 3303.
The published version is available at https://doi.org/10.1038/ncomms4303. Copyright © Jiang et al.