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ABRO1 arrests cardiomyocyte proliferation and myocardial repair by suppressing PSPH

Tao Wang1, Lu-Yu Zhou2, Xin-Min Li2

  • 1Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China; Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|January 14, 2023
PubMed

Insights

Abraxas 2 (ABRO1) regulates cardiomyocyte proliferation and cardiac repair by influencing METTL3-mediated m6A methylation. Its deletion promotes heart regeneration, while its overexpression inhibits it.

Area of Science:

  • Cardiovascular Biology
  • Molecular and Cellular Cardiology
  • Epigenetics

Background:

  • The role of Abraxas 2 (ABRO1) in cardiomyocyte proliferation and myocardial regeneration remains unclear.
  • ABRO1 is a component of the lysine63-linked deubiquitinating system.

Purpose of the Study:

  • To investigate the function of ABRO1 in cardiomyocyte proliferation and cardiac regeneration.
  • To elucidate the molecular mechanism by which ABRO1 regulates these processes.

Main Methods:

  • Investigated ABRO1's role in mouse models with ABRO1 deletion or overexpression.
  • Analyzed cardiomyocyte proliferation, cardiac function after myocardial injury, and molecular pathways involving METTL3, m6A methylation, Psph mRNA, and CDK2 phosphorylation.

Main Results:

  • ABRO1 deletion enhanced cardiomyocyte proliferation and restored heart function post-injury.
  • ABRO1 overexpression inhibited neonatal cardiomyocyte proliferation and cardiac regeneration.
  • ABRO1 regulates cardiomyocyte proliferation via METTL3-mediated Psph mRNA methylation and subsequent CDK2 phosphorylation, controlling cell cycle progression.

Conclusions:

  • ABRO1 is crucial for cell cycle withdrawal and reduced proliferation in postnatal cardiomyocytes.
  • ABRO1 acts as a negative regulator of cardiac regeneration.
  • ABRO1 represents a potential therapeutic target for enhancing cardiomyocyte proliferation and cardiac repair in adult hearts.
Keywords:
ABRO1METTL3PSPHcardiomyocyte proliferationm(6)A methylation

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