JMJD3 inhibition protects against isoproterenol-induced cardiac hypertrophy by suppressing β-MHC expression

Molecular and Cellular Endocrinology
Zhen GuoPeiqing Liu

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.

Citations

Nov 9, 2019·Protein & Cell·Xiangxian ZhangXiawei Wei
Jan 24, 2019·Frontiers in Pharmacology·Zhenzhen LiPeiqing Liu
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Panxia WangPeiqing Liu
Jun 4, 2021·Journal of Molecular and Cellular Cardiology·Kathryn DavisSarah Franklin
Jun 8, 2021·Acta Pharmaceutica Sinica. B·Zhenzhen LiPeiqing Liu
Jun 28, 2021·Journal of Molecular and Cellular Cardiology·Jian QinZhihua Wang

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