Abstract: TH-PO017
Tet2 Contributes to Repression of Cisplatin-Induced AKI by Regulating Metabolic Pathway and Inflammation Response
Session Information
- AKI: Mechanisms - Primary Injury and Repair - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Bai, Mengqiu, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- Han, Fei, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- Chen, Jianghua, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Background
Ten eleven translocation (Tet) methylcytosine dioxygenase family members is known to catalyze 5-methylcytosine to 5-hydroxymethylcytosineas. Previous studies have demonstrated that Tet2 was involved in various pathological process, including leukemia, atherosclerotic cardiovascular diseases and inflammation. However, the role of Tet2 in AKI remains largely unknown.
Methods
We established AKI animal model by Intraperitoneal injecting 22mg/kg cisplatin into male C57BL/6 mice. To explore the role of Tet2 in cisplatin-induced AKI, we generated Tet2 systemic knockout mice by using the cre-loxp system. Serum creatinine and BUN were measured in Tet2-/- mice at 48h and 72h after cisplatin injection to indicate the renal functional changes. 2mg/kg mouse Tet2 catalytic domain expression vector or Tet2 mutant catalytic domain vector or empty vector was administered intravenously for 3 days before cisplatin treatment by hydrodynamic based gene transfer technique to investigate the role of Tet2 in cisplatin-induced AKI. To broaden the role of Tet2 in repressing renal injury caused by cisplatin, we analysed dynamic expression patterns of different genes in renal RNA sequencing (RNA-seq) data of healthy and cisplatin-injected mouse.
Results
We found that Tet2 is highly expressed in healthy kidney and decreased in cisplatin-induced AKI. Exacerbation of cisplatin-induced AKI in Tet2 knock-out mice, and also administration of the Tet2 plasmid could protect Tet2 deficient mice from cisplatin-induced nephrotoxicity. Additionally, renal sequencing results showed that in cisplatin-induced AKI, Tet2 deletion was associated with down-regulation of metabolic-related genes such as the PPAR pathway and increased expression of inflammatory cytokines.
Conclusion
Tet2 may play a role in cisplatin-induced AKI by modulating metabolic and inflammatory responses.