Elucidating the renal injury effects of uranium exposure based on a human kidney organoid model
10.13491/j.issn.1004-714X.2025.06.015
- VernacularTitle:基于人源肾类器官模型解析铀暴露的肾脏损伤效应
- Author:
Ailin TAN
1
;
Yu HUANG
1
;
Jian CHU
2
;
Shaoyu ZHANG
3
;
Zhixia HAN
4
;
Libing YU
2
Author Information
1. Institute of Materials, China Academy of Engineering Physics, Mianyang 621907 , China;School of Public Health, Southwest Medical University, Luzhou 646600, China.
2. Institute of Materials, China Academy of Engineering Physics, Mianyang 621907 , China.
3. 903 Hospital, Mianyang 621700, China.
4. School of Public Health, Southwest Medical University, Luzhou 646600, China;Environmental Health Effects And Risk Assessment KeyLaboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 646000, China.
- Publication Type:OriginalArticles
- Keywords:
Kidney organoid;
Uranyl ion;
Metabolomics;
Oxidative stress;
Mitochondrial dysfunction;
Apoptosis
- From:
Chinese Journal of Radiological Health
2025;34(6):871-879
- CountryChina
- Language:Chinese
-
Abstract:
Objective Uranium compounds are critical materials in the nuclear industry, and their mining, processing, and use pose occupational exposure risks. Epidemiological studies have shown that uranium exposure can impair health, with acute uranium poisoning primarily causing structural and functional damage to the kidneys. Currently, the molecular mechanisms underlying uranium-induced kidney injury remain unclear, and traditional biological models used in toxicological research are inadequate for simulating the human microenvironment. This study employed a human kidney organoid model system to elucidate the nephrotoxic mechanisms of uranyl ions, providing a scientific basis for the prevention and control of uranium poisoning. Methods Kidney organoids were constructed using the human embryonic stem cell line H1 and exposed to solutions with different uranyl ion concentrations. Morphological observation, ATP detection, reactive oxygen species detection, apoptosis assay, and untargeted metabolomics analysis were performed. Mechanisms of toxicity were further explored through KEGG pathway enrichment analysis. Results Uranium exposure led to structural damage in the organoids, accompanied by a dose-dependent decrease in ATP levels, accumulation of reactive oxygen species, and increased apoptosis rate. After 24-hour exposure to 300 μmol/L uranium, significantly disturbed differential metabolites and five core metabolic pathways were identified. Conclusion Uranium induces oxidative stress, mitochondrial dysfunction (ATP reduction), and metabolic disorder (disruption of phospholipid/amino acid metabolism), which synergistically cause DNA damage, apoptosis, and/or necrosis. These findings provide new insights into the mechanisms of uranium-induced kidney injury and support the development of prevention and control strategies.
