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Updated: Oct 29, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury
Yinwu Bao1,2,3, Mengqiu Bai1,2,3, Huanhuan Zhu1
1The Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine; Institute of Nephrology, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, 310003, China.
Abstract:
Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers' expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.
Insights
The demethylase Tet2 (Tet2) enzyme protects against acute kidney injury (AKI). Tet2 deficiency worsens kidney damage and inflammation, while its presence offers renal protection via metabolic and inflammatory pathways.
Area of Science:
- * Molecular Biology
- * Immunology
- * Nephrology
Background:
- * The enzyme Tet2 is crucial for immune responses.
- * Acute kidney injury (AKI) involves inflammation and cellular damage.
- * The specific role of Tet2 in AKI pathogenesis is not well understood.
Purpose of the Study:
- * To investigate the role of Tet2 in the development of acute kidney injury.
- * To determine the effect of Tet2 gene expression levels on renal tissue damage.
- * To elucidate the protective mechanisms of Tet2 in AKI.
Main Methods:
- * A cisplatin-induced acute kidney injury mouse model was utilized.
- * Tet2-knockout (KO) mice and wild-type mice were compared.
- * Tet2 plasmid administration was used to assess protective effects.
Main Results:
- * Tet2-KO mice exhibited exacerbated tubular necrosis, dilatation, and inflammation post-cisplatin treatment.
- * Tet2 plasmid administration conferred protection against cisplatin-induced nephrotoxicity in KO mice.
- * Tet2 deficiency altered metabolic pathways, including retinol and arachidonic acid metabolism, and PPAR signaling.
Conclusions:
- * Tet2 plays a significant renal protective role in acute kidney injury.
- * Tet2 mitigates AKI by regulating metabolic and inflammatory responses, particularly through the PPAR signaling pathway.
- * Tet2 expression is downregulated in various AKI models and clinical samples, highlighting its therapeutic potential.
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