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Updated: Oct 18, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by Attenuating Programmed Cell Death and Inflammation
Qin Yang1, Li Gao1, Xiao-Wei Hu1
1Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China.
Background:
Transforming growth factor-β (TGF-β)/Smad signaling is the central mediator in renal fibrosis, yet its functional role in acute kidney injury (AKI) is not fully understood. Recent evidence showed that TGF-β/Smad3 may be involved in the pathogenesis of AKI, but its functional role and mechanism of action in cisplatin-induced AKI are unclear.
Objectives:
Demonstrating that Smad3 may play certain roles in cisplatin nephropathy due to its potential effect on programmed cell death and inflammation.
Methods:
Here, we established a cisplatin-induced AKI mouse model with Smad3 knockout mice and created stable in vitro models with Smad3 knockdown tubular epithelial cells. In addition, we tested the potential of Smad3-targeted therapy using 2 in vivo protocols - lentivirus-mediated Smad3 silencing in vivo and use of naringenin, a monomer used in traditional Chinese medicine and a natural inhibitor of Smad3.
Results:
Disruption of Smad3 attenuated cisplatin-induced kidney injury, inflammation, and NADPH oxidase 4-dependent oxidative stress. We found that Smad3-targeted therapy protected against loss of renal function and alleviated apoptosis, RIPK-mediated necroptosis, renal inflammation, and oxidative stress in cisplatin nephropathy.
Conclusions:
These findings show that Smad3 promotes cisplatin-induced AKI and Smad3-targeted therapy protects against this pathological process. These findings have substantial clinical relevance, as they suggest a therapeutic target for AKI.
Insights
Smad3 promotes cisplatin-induced acute kidney injury (AKI). Targeting Smad3 with therapies like naringenin protects kidney function by reducing inflammation and cell death, suggesting Smad3 as a therapeutic target for AKI.
Area of Science:
- Nephrology
- Molecular Biology
- Cellular Biology
Background:
- Transforming growth factor-β (TGF-β)/Smad signaling is key in renal fibrosis.
- The role of TGF-β/Smad3 in acute kidney injury (AKI), particularly cisplatin-induced AKI, remains unclear.
- Smad3's involvement in programmed cell death and inflammation in AKI warrants investigation.
Purpose of the Study:
- To investigate the functional role of Smad3 in cisplatin-induced AKI.
- To explore the potential of Smad3-targeted therapy for treating cisplatin nephropathy.
Main Methods:
- Established cisplatin-induced AKI mouse models using Smad3 knockout mice.
- Created in vitro models with Smad3 knockdown tubular epithelial cells.
- Evaluated Smad3-targeted therapies including lentivirus-mediated Smad3 silencing and naringenin treatment.
Main Results:
- Smad3 disruption attenuated kidney injury, inflammation, and oxidative stress in cisplatin-induced AKI.
- Smad3-targeted therapy improved renal function and reduced apoptosis and necroptosis.
- Therapies alleviated inflammation and oxidative stress in cisplatin nephropathy.
Conclusions:
- Smad3 plays a promoting role in cisplatin-induced AKI.
- Smad3-targeted therapy demonstrates protective effects against cisplatin nephropathy.
- These findings highlight Smad3 as a potential therapeutic target for AKI.
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