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

Zhen Guo1, Jing Lu2, Jingyan Li1

  • 1Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China; National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.

Molecular and Cellular Endocrinology
|May 13, 2018
PubMed

Insights

Jumonji domain-containing protein D3 (JMJD3) promotes cardiac hypertrophy by regulating histone methylation. Inhibiting JMJD3 or its demethylase activity may offer a therapeutic strategy for heart conditions.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Molecular Medicine

Background:

  • Jumonji domain-containing protein D3 (JMJD3) is a histone demethylase involved in development and disease.
  • Its role in the cardiovascular system, particularly cardiac hypertrophy, is largely unexplored.

Purpose of the Study:

  • To investigate the role of JMJD3 in cardiac hypertrophy.
  • To elucidate the molecular mechanisms underlying JMJD3's function in the heart.

Main Methods:

  • Studied JMJD3 expression in response to isoproterenol (ISO) in vitro and in vivo.
  • Utilized gain-of-function (overexpression) and loss-of-function (silencing, inhibitor GSK-J4) approaches.
  • Assessed cardiomyocyte size and hypertrophy marker gene expression.
  • Investigated JMJD3 recruitment and histone 3 lysine 27 trimethylation (H3K27me3) at the β-myosin heavy chain (β-MHC) promoter.

Main Results:

  • JMJD3 expression increased with ISO stimuli.
  • JMJD3 overexpression promoted cardiomyocyte hypertrophy and hypertrophy marker genes.
  • JMJD3 silencing or inhibition with GSK-J4 attenuated ISO-induced hypertrophy.
  • JMJD3 demethylated H3K27me3 at the β-MHC promoter, enhancing its expression.

Conclusions:

  • JMJD3 plays a critical role in cardiac hypertrophy.
  • JMJD3 acts as an epigenetic regulator of β-MHC expression in cardiomyocytes.
  • JMJD3 represents a potential therapeutic target for cardiac hypertrophy.

Keywords:
Cardiac hypertrophyGSK-J4IsoproterenolJMJD3β-MHC

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