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IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice

Author

Listed:
  • Zhen-Guo Ma

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Yu-Pei Yuan

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Di Fan

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Xin Zhang

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Teng Teng

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Peng Song

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Chun-Yan Kong

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Can Hu

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Wen-Ying Wei

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

  • Qi-Zhu Tang

    (Renmin Hospital of Wuhan University
    Cardiovascular Research Institute of Wuhan University
    Hubei Key Laboratory of Metabolic and Chronic Diseases)

Abstract

Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.

Suggested Citation

  • Zhen-Guo Ma & Yu-Pei Yuan & Di Fan & Xin Zhang & Teng Teng & Peng Song & Chun-Yan Kong & Can Hu & Wen-Ying Wei & Qi-Zhu Tang, 2023. "IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40639-6
    DOI: 10.1038/s41467-023-40639-6
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    1. Yan-Xiao Ji & Peng Zhang & Xiao-Jing Zhang & Yi-Chao Zhao & Ke-Qiong Deng & Xi Jiang & Pi-Xiao Wang & Zan Huang & Hongliang Li, 2016. "The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling," Nature Communications, Nature, vol. 7(1), pages 1-20, September.
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    Cited by:

    1. Xin Zhang & Yi-Peng Gao & Wen-Sheng Dong & Kang Li & Yu-Xin Hu & Yun-Jia Ye & Can Hu, 2024. "FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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