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Updated: Jul 2, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Identification of TACSTD2 as novel therapeutic targets for cisplatin-induced acute kidney injury by multi-omics data
Zebin Deng1, Zheng Dong2,3, Yinhuai Wang1
1Department of Urology, The Second Xiangya Hospital at Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Abstract:
Cisplatin-induced acute kidney injury (CP-AKI) is a common complication in cancer patients. Although ferroptosis is believed to contribute to the progression of CP-AKI, its mechanisms remain incompletely understood. In this study, after initially processed individual omics datasets, we integrated multi-omics data to construct a ferroptosis network in the kidney, resulting in the identification of the key driver TACSTD2. In vitro and in vivo results showed that TACSTD2 was notably upregulated in cisplatin-treated kidneys and BUMPT cells. Overexpression of TACSTD2 accelerated ferroptosis, while its gene disruption decelerated ferroptosis, likely mediated by its potential downstream targets HMGB1, IRF6, and LCN2. Drug prediction and molecular docking were further used to propose that drugs targeting TACSTD2 may have therapeutic potential in CP-AKI, such as parthenolide, progesterone, premarin, estradiol and rosiglitazone. Our findings suggest a significant association between ferroptosis and the development of CP-AKI, with TACSTD2 playing a crucial role in modulating ferroptosis, which provides novel perspectives on the pathogenesis and treatment of CP-AKI.
Insights
This study reveals TACSTD2 as a key driver in cisplatin-induced acute kidney injury (CP-AKI) by modulating ferroptosis. Targeting TACSTD2 offers potential new treatments for CP-AKI.
Area of Science:
- Nephrology
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cisplatin-induced acute kidney injury (CP-AKI) is a significant clinical challenge in cancer therapy.
- The precise mechanisms by which ferroptosis contributes to CP-AKI progression are not fully elucidated.
Purpose of the Study:
- To integrate multi-omics data to construct a ferroptosis network in the kidney and identify key regulatory factors in CP-AKI.
- To investigate the role of TACSTD2 in ferroptosis and its potential as a therapeutic target for CP-AKI.
Main Methods:
- Integrated multi-omics data analysis to build a kidney ferroptosis network.
- In vitro and in vivo experiments to assess TACSTD2 expression and function in cisplatin-treated kidney cells and tissues.
- Analysis of potential downstream targets (HMGB1, IRF6, LCN2) of TACSTD2.
- In silico drug prediction and molecular docking to identify potential therapeutic agents targeting TACSTD2.
Main Results:
- TACSTD2 was identified as a key driver in the kidney ferroptosis network associated with CP-AKI and was upregulated in cisplatin-treated kidneys and BUMPT cells.
- TACSTD2 overexpression exacerbated ferroptosis, while gene disruption attenuated it, suggesting a critical role in ferroptosis regulation.
- Potential downstream targets HMGB1, IRF6, and LCN2 were implicated in TACSTD2-mediated ferroptosis.
- Several drugs, including parthenolide, progesterone, premarin, estradiol, and rosiglitazone, were predicted to target TACSTD2 for potential CP-AKI therapy.
Conclusions:
- Ferroptosis is significantly associated with the pathogenesis of CP-AKI.
- TACSTD2 plays a pivotal role in regulating ferroptosis in the context of CP-AKI.
- Targeting TACSTD2 presents a promising therapeutic strategy for mitigating CP-AKI.
