Abstract: TH-PO0156
Analysis of Lipidomics and Transcriptomics Reveals the Mechanisms of Cisplatin-Induced Nephrotoxicity in Old Mice
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Li, Guoli, Department of Nephrology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
- Tan, Huifang, Department of Nephrology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
- Xie, Tingting, Department of General Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Chen, Yinyin, Department of Nephrology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
Background
Clinical studies indicate that elderly patients are more susceptible to cisplatin-induced nephrotoxicity and acute kidney injury (AKI), and have lower long-term survival. However, the exact molecular mechanism underlying remains unclear. The objective of this study was to examine the impact of the cisplatin treatment on the lipidome and transcriptome associated with aging in mouse kidney.
Methods
In this study, we used cisplatin-challenged (20 mg/kg) young C57BL/6 mice (3 months) and aging C57BL/6 mice (24 months) as cisplatin induced AKI models. RNA sequencing and untargeted LC-MS lipidomics was conducted to establish multi-omics signatures of transcriptomic regulation and lipid remodeling.
Results
In total, 4394 lipid species from 44 lipid classes were identified. 374 metabolites were significantly different between young and old group without cisplatin treatment, and 566 metabolites were significantly different between young and old group with cisplatin treatment. Lipidomic analysis shows that aging did not lead to changes of the overall composition of lipid classes. RNA sequencing showed that compare to young mouse kidney, 114 more gene were differentially expressed in old mouse kidney upon cisplatin treatment. These genes involved in pathways, such as arginine biosynthesis, fatty acid biosynthesis, endocrine and other factor−regulated calcium reabsorption and renin−angiotensin system. Integrated transcriptomic and lipidomic analysis identified candidate enzymes responsible for the change of lipid profiles in aged mice. In old mice, a small number of genetic changes caused a strong response to lipid components upon cisplatin treatment.
Conclusion
Our study offers new insights into the molecular mechanisms of aging-related lipid remodeling in the kidney, possibly through which cisplatin induces renal damage. These findings may serve as a comprehensive resource for future studies on cisplatin-induced nephrotoxicity in the setting of aging.
Funding
- Government Support – Non-U.S.