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A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury

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Listed:
  • Chen Yang

    (Huazhong University of Science and Technology)

  • Huidie Xu

    (Huazhong University of Science and Technology)

  • Dong Yang

    (Huazhong University of Science and Technology
    Wuhan University)

  • Yunhao Xie

    (Wuhan University)

  • Mingrui Xiong

    (Huazhong University of Science and Technology)

  • Yu Fan

    (Wuhan University)

  • XiKai Liu

    (Wuhan University)

  • Yu Zhang

    (Huazhong University of Science and Technology)

  • Yushuo Xiao

    (Huazhong University of Science and Technology)

  • Yuchen Chen

    (Huazhong University of Science and Technology)

  • Yihao Zhou

    (Wuhan University)

  • Liangliang Song

    (Huazhong University of Science and Technology)

  • Chen Wang

    (Huazhong University of Science and Technology)

  • Anlin Peng

    (Tongren Hospital of Wuhan University)

  • Robert B. Petersen

    (Central Michigan University College of Medicine)

  • Hong Chen

    (Huazhong University of Science and Technology)

  • Kun Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Ling Zheng

    (Wuhan University)

Abstract

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.

Suggested Citation

  • Chen Yang & Huidie Xu & Dong Yang & Yunhao Xie & Mingrui Xiong & Yu Fan & XiKai Liu & Yu Zhang & Yushuo Xiao & Yuchen Chen & Yihao Zhou & Liangliang Song & Chen Wang & Anlin Peng & Robert B. Petersen , 2023. "A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40036-z
    DOI: 10.1038/s41467-023-40036-z
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    Cited by:

    1. Xi Li & Linwei Yu & Xikai Liu & Tianyi Shi & Yu Zhang & Yushuo Xiao & Chen Wang & Liangliang Song & Ning Li & Xinran Liu & Yuchen Chen & Robert B. Petersen & Xiang Cheng & Weikang Xue & Yanxun V. Yu &, 2024. "β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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