Abstract: FR-PO172
USP13 Targets MCL-1 to Protect Mitochondria-Attenuating AKI
Session Information
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wang, Qian, Nanjing Medical University, Nanjing, Jiangsu, China
- Xia, Weiwei, Nanjing Medical University, Nanjing, Jiangsu, China
- Zhang, Yue, Nanjing Medical University, Nanjing, Jiangsu, China
- Zhang, Aihua, Nanjing Medical University, Nanjing, Jiangsu, China
- Jia, Zhanjun, Nanjing Medical University, Nanjing, Jiangsu, China
Background
Acute kidney injury （AKI）is a severe clinical syndrome with high mortality. Thus, investigation on its mechanism and drugable targets is of importance. Here we investigated the novel role and mechanism of ubiquitin specific proteases 13 (USP13) in AKI.
Methods
Eight weeks old WT and USP13+/- mice were subjected to cisplatin and folic acid (FA) to induce AKI. Rapid injection of USP13 plasmids via tail vein was applied to overexpress USP13 in kidney. The serum and kidney tissues were collected for analysis. In vitro cells were used for the mechanistic study.
Results
Immunofluorescence showed that USP13 was expressed in the kidney tubular epithelial cell of human and mouse. In WT mice, cisplatin or FA strikingly enhanced serum BUN, Cys C and Cr, which were further enhanced in USP13+/- mice by around 15% to 30%, respectively. Meanwhile, USP13+/- mice with AKI showed aggravated mitochondrial injury in kidney. In contrast, overexpression of USP13 in kidney significantly protected against AKI and mitochondrial damage. Furthermore, the mechanistic study suggested that USP13 deubiquitinated and stabilized myeloid cell leukelia-l (MCL-1) to protect mitochondria under AKI, thus resulting in a protection against AKI. Finally, pharmacological inhibition of USP13 by spautin-1 (10mg/kg, I.P., daily) also worsened AKI.
Conclusion
USP13 could deubiquitinate and stabilize MCL-1 to protect against mitochondrial injury and AKI. Targeting USP13 could be a potential strategy in treating AKI.