Frontiers in Cell and Developmental Biology (Oct 2021)
Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
- Mengying Wu,
- Mengying Wu,
- Mengying Wu,
- Weiwei Xia,
- Weiwei Xia,
- Weiwei Xia,
- Qianqian Jin,
- Qianqian Jin,
- Qianqian Jin,
- Anning Zhou,
- Anning Zhou,
- Anning Zhou,
- Qian Wang,
- Qian Wang,
- Qian Wang,
- Shuzhen Li,
- Shuzhen Li,
- Shuzhen Li,
- Songming Huang,
- Songming Huang,
- Songming Huang,
- Aihua Zhang,
- Aihua Zhang,
- Aihua Zhang,
- Yue Zhang,
- Yue Zhang,
- Yue Zhang,
- Yuanyuan Li,
- Yuanyuan Li,
- Yuanyuan Li,
- Zhanjun Jia,
- Zhanjun Jia,
- Zhanjun Jia
Affiliations
- Mengying Wu
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Mengying Wu
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Mengying Wu
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Weiwei Xia
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Weiwei Xia
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Weiwei Xia
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Qianqian Jin
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Qianqian Jin
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Qianqian Jin
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Anning Zhou
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Anning Zhou
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Anning Zhou
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Qian Wang
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Qian Wang
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Qian Wang
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Shuzhen Li
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Shuzhen Li
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Shuzhen Li
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Songming Huang
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Songming Huang
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Songming Huang
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Aihua Zhang
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Aihua Zhang
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Aihua Zhang
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Yue Zhang
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Yue Zhang
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Yue Zhang
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Yuanyuan Li
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Yuanyuan Li
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Yuanyuan Li
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- Zhanjun Jia
- Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Zhanjun Jia
- Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Zhanjun Jia
- Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China
- DOI
- https://doi.org/10.3389/fcell.2021.754134
- Journal volume & issue
-
Vol. 9
Abstract
Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs.
Keywords