MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production
Uranium poisoning, particularly from exposure to Depleted Uranium (DU), occurs when uranyl ions enter the bloodstream and bind primarily to transferrin, osteopontin, and albumin before entering cells via corresponding receptors on renal tubular membranes, leading to cellular damage. Uranium poisonin...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324017305 |
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| author | Xinrui Yang Jing Liu Yaru Yin Luxun Yang Mingquan Gao Zifei Wu Binghui Lu Shenglin Luo Weidong Wang Rong Li |
| author_facet | Xinrui Yang Jing Liu Yaru Yin Luxun Yang Mingquan Gao Zifei Wu Binghui Lu Shenglin Luo Weidong Wang Rong Li |
| author_sort | Xinrui Yang |
| collection | DOAJ |
| description | Uranium poisoning, particularly from exposure to Depleted Uranium (DU), occurs when uranyl ions enter the bloodstream and bind primarily to transferrin, osteopontin, and albumin before entering cells via corresponding receptors on renal tubular membranes, leading to cellular damage. Uranium poisoning remains a significant clinical challenge, with no ideal treatment currently available. In this study, we investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cell exosomes (MSC-EXs) in mice exposed to DU. Our results showed that MSC-EXs could ameliorate renal damage and enhance kidney and bone marrow morphology but also effectively promote uranium excretion while reducing internal retention. Notably, the protective effects of MSC-EXs exceed those of MSCs and are comparable to those of sodium bicarbonate, as confirmed by various analytical techniques. Proteomic studies have shown that MSC-EXs reduce uranyl ion deposition in renal tubule cells through competitive binding with transferrin, osteopontin, and albumin. They also enhance oxidative stress resistance via modulation of glutathione metabolism, Cysteine and Methionine metabolism signaling pathways. This regulation leads to a reduction in mitochondrial ROS production, alleviates lipid peroxidation, and consequently decreases cellular apoptosis and ferroptosis. This study identifies MSC-EXs as a novel therapeutic strategy against depleted uranium poisoning, presenting potential advancements in treatment methodologies. |
| format | Article |
| id | doaj-art-bbc530ea732444a7b1b45217b500c7b5 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-bbc530ea732444a7b1b45217b500c7b52025-01-23T05:25:59ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117654MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS productionXinrui Yang0Jing Liu1Yaru Yin2Luxun Yang3Mingquan Gao4Zifei Wu5Binghui Lu6Shenglin Luo7Weidong Wang8Rong Li9Institute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaInstitute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, ChinaDepartment of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China; Corresponding author.Institute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, China; Correspondence to: Army Medical University, No.30 Gaotanyan Street, Chongqing 400038, China.Uranium poisoning, particularly from exposure to Depleted Uranium (DU), occurs when uranyl ions enter the bloodstream and bind primarily to transferrin, osteopontin, and albumin before entering cells via corresponding receptors on renal tubular membranes, leading to cellular damage. Uranium poisoning remains a significant clinical challenge, with no ideal treatment currently available. In this study, we investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cell exosomes (MSC-EXs) in mice exposed to DU. Our results showed that MSC-EXs could ameliorate renal damage and enhance kidney and bone marrow morphology but also effectively promote uranium excretion while reducing internal retention. Notably, the protective effects of MSC-EXs exceed those of MSCs and are comparable to those of sodium bicarbonate, as confirmed by various analytical techniques. Proteomic studies have shown that MSC-EXs reduce uranyl ion deposition in renal tubule cells through competitive binding with transferrin, osteopontin, and albumin. They also enhance oxidative stress resistance via modulation of glutathione metabolism, Cysteine and Methionine metabolism signaling pathways. This regulation leads to a reduction in mitochondrial ROS production, alleviates lipid peroxidation, and consequently decreases cellular apoptosis and ferroptosis. This study identifies MSC-EXs as a novel therapeutic strategy against depleted uranium poisoning, presenting potential advancements in treatment methodologies.http://www.sciencedirect.com/science/article/pii/S0147651324017305Uranium poisoningMesenchymal stem cellsExosomesFerroptosisOxidative resistanceRenal toxicity |
| spellingShingle | Xinrui Yang Jing Liu Yaru Yin Luxun Yang Mingquan Gao Zifei Wu Binghui Lu Shenglin Luo Weidong Wang Rong Li MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production Ecotoxicology and Environmental Safety Uranium poisoning Mesenchymal stem cells Exosomes Ferroptosis Oxidative resistance Renal toxicity |
| title | MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production |
| title_full | MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production |
| title_fullStr | MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production |
| title_full_unstemmed | MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production |
| title_short | MSC-EXs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ROS production |
| title_sort | msc exs inhibits uranium nephrotoxicity by competitively binding key proteins and inhibiting ros production |
| topic | Uranium poisoning Mesenchymal stem cells Exosomes Ferroptosis Oxidative resistance Renal toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324017305 |
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