2. Academic Validation
  3. Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury

Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury

  • Cell Death Discov. 2025 Jul 1;11(1):290. doi: 10.1038/s41420-025-02578-7.
Hong Duo # 1,  Yanwei Yang # 2,  Jun Luo # 1,  Yumeng Cao 3,  Qian Liu 4,  Jiarui Zhang 5,  Siqi Du 1,  Jian You 1,  Guqin Zhang 6,  Qifa Ye 7,  Huaqin Pan 8 9
Affiliations

Affiliations

  • 1 National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei, China.
  • 2 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071, China.
  • 3 Nanchang Hongdu Hospital of Traditional Chinese Medicine, 330006, Jiangxi, China.
  • 4 College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China.
  • 5 Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 6 Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. zgqxiaoxiao@126.com.
  • 7 National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei, China. yqf_china@163.com.
  • 8 National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei, China. phq2012@whu.edu.cn.
  • 9 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplantation Intensive Care Unit, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, China; Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071, China. phq2012@whu.edu.cn.
  • # Contributed equally.
PMID: 40595455 DOI: 10.1038/s41420-025-02578-7
Abstract

Sepsis-associated acute kidney injury (SA-AKI) is a critical condition characterized by high morbidity and mortality rates, particularly in intensive care settings. This study focuses on RP105, a pattern recognition receptor, exploring its role in moderating the mechanisms of oxidative stress and Ferroptosis during SA-AKI, offering insights into its potential as a therapeutic target. SA-AKI model was established using RP105 knockout (KO) and wild-type (WT) mice through cecal ligation and puncture (CLP). Comprehensive evaluations included the assessment of Ferroptosis markers and the expression levels of pro-inflammatory cytokines. RP105 expression was markedly reduced in the kidneys following CLP induction, correlating with worsened renal outcomes. Compared to the Sham group, RP105-/- mice displayed heightened renal damage, increased levels of oxidative stress markers, and enhanced lipid peroxidation. Notably, the deficiency of RP105 led to increased macrophage infiltration and a shift towards pro-inflammatory phenotypes, which further potentiated Ferroptosis and exacerbated renal tissue damage. By influencing macrophage behavior and mitigating inflammatory responses. RP105 deficiency exacerbates macrophage-induced inflammation, oxidative stress, and Ferroptosis, forming a vicious cycle that leads to more severe renal injury. These findings underscore the pivotal role of RP105 in mitigating oxidative stress and suppressing Ferroptosis in the context of SA-AKI through regulation of the HO-1/SLC7A11/GPX4 axis. By preventing macrophage polarization toward a pro-inflammatory phenotype, RP105 alleviates inflammatory responses and tissue damage, highlighting its potential as a therapeutic target. Thus, RP105 emerges as a promising therapeutic candidate for mitigating sepsis-induced renal damage.

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