Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury
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 stre...
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02578-7 |
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| author | Hong Duo Yanwei Yang Jun Luo Yumeng Cao Qian Liu Jiarui Zhang Siqi Du Jian You Guqing Zhang Qifa Ye Huaqin Pan |
| author_facet | Hong Duo Yanwei Yang Jun Luo Yumeng Cao Qian Liu Jiarui Zhang Siqi Du Jian You Guqing Zhang Qifa Ye Huaqin Pan |
| author_sort | Hong Duo |
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| description | 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. |
| format | Article |
| id | doaj-art-0deb7f32c92d4aa6892d228097f321f5 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
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| series | Cell Death Discovery |
| spelling | doaj-art-0deb7f32c92d4aa6892d228097f321f52025-08-20T03:45:24ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111510.1038/s41420-025-02578-7Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injuryHong Duo0Yanwei Yang1Jun Luo2Yumeng Cao3Qian Liu4Jiarui Zhang5Siqi Du6Jian You7Guqing Zhang8Qifa Ye9Huaqin Pan10National 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 UniversityDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Clinical Research Center of Hubei Critical Care MedicineNational 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 UniversityNanchang Hongdu Hospital of Traditional Chinese MedicineCollege of Life Sciences, Wuhan UniversityDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan UniversityNational 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 UniversityNational 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 UniversityDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan UniversityNational 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 UniversityNational 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 UniversityAbstract 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.https://doi.org/10.1038/s41420-025-02578-7 |
| spellingShingle | Hong Duo Yanwei Yang Jun Luo Yumeng Cao Qian Liu Jiarui Zhang Siqi Du Jian You Guqing Zhang Qifa Ye Huaqin Pan 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 Discovery |
| title | Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury |
| title_full | Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury |
| title_fullStr | Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury |
| title_full_unstemmed | Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury |
| title_short | Modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the HO-1/SLC7A11/GPX4 axis in sepsis-mediated renal injury |
| title_sort | modulatory role of radioprotective 105 in mitigating oxidative stress and ferroptosis via the ho 1 slc7a11 gpx4 axis in sepsis mediated renal injury |
| url | https://doi.org/10.1038/s41420-025-02578-7 |
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