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<p>Acute kidney injury (AKI) is a common, clinical syndrome caused by multiple factors. The high mortality rate, high cost of treatment, and the potential for progression to chronic kidney disease (CKD) make AKI an important global public health problem. Glutathione peroxidase 4 (GPX4), a key intracellular regulator, is involved in antioxidant defense mechanisms and ferroptosis pathways. Existing studies have demonstrated that ferroptosis is closely related to the development of AKI, and GPX4, as a major ferroptosis inhibitor, plays an important role in the disease process. In this review, we reviewed the literature on the role of GPX4 in various animal models of AKI, summarized the possible mechanisms by which GPX4 affects the disease process (oxidative stress, ferroptosis, and signaling, etc.), emphasized that antioxidants, ferroptosis inhibitors, and some novel nanomaterials affect the disease process by influencing the expression and activity of GPX4, and explored the potential of GPX4 as a potential target for AKI therapy.</p><p><?noindent??><b>Clinical trial number</b> Not applicable.</p> Graphical Abstract <p></p>

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Molecular mechanisms and therapeutic strategies of GPX4 regulation in acute kidney injury

  • 期刊论文

  • 发表日期：

    2025年8月28日

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  • Zhidan Shi,
  • Chu Zhang,
  • Tian Xie,
  • Jie Song,
  • Xiaoqian Zeng,
  • Jiayi Hu,
  • Xinqi He,
  • Qingyang Zhang,
  • Shuting Chen,
  • Xinpeng Zhou,
  • Guangzhe Yao,
  • Ling He

摘要

Acute kidney injury (AKI) is a common, clinical syndrome caused by multiple factors. The high mortality rate, high cost of treatment, and the potential for progression to chronic kidney disease (CKD) make AKI an important global public health problem. Glutathione peroxidase 4 (GPX4), a key intracellular regulator, is involved in antioxidant defense mechanisms and ferroptosis pathways. Existing studies have demonstrated that ferroptosis is closely related to the development of AKI, and GPX4, as a major ferroptosis inhibitor, plays an important role in the disease process. In this review, we reviewed the literature on the role of GPX4 in various animal models of AKI, summarized the possible mechanisms by which GPX4 affects the disease process (oxidative stress, ferroptosis, and signaling, etc.), emphasized that antioxidants, ferroptosis inhibitors, and some novel nanomaterials affect the disease process by influencing the expression and activity of GPX4, and explored the potential of GPX4 as a potential target for AKI therapy.

Clinical trial number Not applicable.

Graphical Abstract