1. JMJD3 inhibition protects against isoproterenol-induced cardiac hypertrophy by suppressing β-MHC expression.
- Author
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Guo, Zhen, Lu, Jing, Li, Jingyan, Wang, Panxia, Li, Zhenzhen, Zhong, Yao, Guo, Kaiteng, Wang, Junjian, Ye, Jiantao, and Liu, Peiqing
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HISTONE demethylases , *LYSINE specific demethylase 1 , *CELL physiology , *CARDIAC hypertrophy , *PROTEIN expression - Abstract
Abstract Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes. In contrary, JMJD3 silencing or its inhibitor GSK-J4 suppressed ISO-induced cardiac hypertrophy. Mechanistically, JMJD3 was recruited to demethylate H3K27me3 at the promoter of β-MHC to promote its expression and cardiac hypertrophy. Thus, our results reveal that JMJD3 may be a key epigenetic regulator of β-MHC expression in cardiomyocytes and a potential therapeutic target for cardiac hypertrophy. Graphical abstract Image 1 Highlights • JMJD3 expression was significantly upregulated in ISO-induced cardiac hypertrophy in vitro and in vivo. • JMJD3 depletion or GSK-J4 treatment attenuated the hypertrophic responses stimulated by ISO. • JMJD3 overexpression led to cardiac hypertrophy. • JMJD3 was recruited to and demethylated H3K27me3 at the promoter of β-MHC to promote its expression and cardiac hypertrophy. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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