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Cardiomyocyte-derived USP13 protects hearts from hypertrophy via deubiquitinating and stabilizing STAT1 in male mice

Author

Listed:
  • Jibo Han

    (the First Affiliated Hospital of Wenzhou Medical University
    Hangzhou Normal University
    the Second Affiliated Hospital of Jiaxing University)

  • Liming Lin

    (Wenzhou Medical University)

  • Zimin Fang

    (the First Affiliated Hospital of Wenzhou Medical University)

  • Diyun Xu

    (the First Affiliated Hospital of Wenzhou Medical University)

  • Lintao Wang

    (Nanjing University)

  • Bozhi Ye

    (the First Affiliated Hospital of Wenzhou Medical University)

  • Xue Han

    (Hangzhou Medical College)

  • Xiaohong Long

    (Nanjing University)

  • Julian Min

    (Hangzhou Medical College)

  • Gaojun Wu

    (the First Affiliated Hospital of Wenzhou Medical University)

  • Guang Liang

    (the First Affiliated Hospital of Wenzhou Medical University
    Wenzhou Medical University
    Hangzhou Medical College)

  • Yi Wang

    (the First Affiliated Hospital of Wenzhou Medical University
    Hangzhou Normal University
    Wenzhou Medical University)

Abstract

Cardiac hypertrophy leads to ventricular dysfunction and heart failure. Deubiquitinating enzymes are responsible for preserving the substrate protein stability and are essential to myocardial hypertrophy. In this study, we aimed to explore the role and regulatory mechanism of a cardiomyocyte-derived deubiquitinating enzyme, USP13, in cardiac hypertrophy. Here we show that USP13 was increased in hypertrophic myocardium and was mainly distributed in cardiomyocytes. Cardiomyocyte-specific Usp13 knockout aggravated TAC or Ang II-induced myocardial hypertrophy and dysfunction in male mice. Correspondingly, USP13 overexpression by AAV9 in hearts exerted a therapeutic impact on cardiac hypertrophy in male mice. Mechanistically, we identified STAT1 as a substrate of USP13 through interactome analysis. USP13 deubiquitinated STAT1, thereby reducing its degradation. Subsequently, USP13 promoted the STAT1-targeted Nppb gene transcription and enhanced mitochondrial function in cardiomyocytes. This study illustrated a beneficial effect of USP13 in hypertrophic cardiomyocytes and identified a cardiomyocyte-specific USP13-STAT1 axis in regulating cardiac hypertrophy.

Suggested Citation

  • Jibo Han & Liming Lin & Zimin Fang & Diyun Xu & Lintao Wang & Bozhi Ye & Xue Han & Xiaohong Long & Julian Min & Gaojun Wu & Guang Liang & Yi Wang, 2025. "Cardiomyocyte-derived USP13 protects hearts from hypertrophy via deubiquitinating and stabilizing STAT1 in male mice," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61028-1
    DOI: 10.1038/s41467-025-61028-1
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    References listed on IDEAS

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    1. He Sun & Qiang Zhang & Ying-Ying Jing & Man Zhang & Hai-Ying Wang & Zeng Cai & Tianzi Liuyu & Zhi-Dong Zhang & Tian-Chen Xiong & Yan Wu & Qi-Yun Zhu & Jing Yao & Hong-Bing Shu & Dandan Lin & Bo Zhong, 2017. "USP13 negatively regulates antiviral responses by deubiquitinating STING," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    2. Xiansi Zhao & Brian Fiske & Akinori Kawakami & Juying Li & David E Fisher, 2011. "Regulation of MITF stability by the USP13 deubiquitinase," Nature Communications, Nature, vol. 2(1), pages 1-8, September.
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