Abstract: FR-PO177
Renal Tubular Epithelial Cells RIPK3 Promote AKI Progressing to CKD
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
- Xie, Zhiyong, Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Dong, Wei, Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Chen, Yingwen, Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Li, Luan, Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Liang, Xinling, Division of Nephrology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Background
Acute kidney injury (AKI) could increase the risk of long-term chronic kidney diseases (CKD) but its exact mechanism is still unclear. The purpose of this study was to clarify the role and mechanism of renal tubular epithelial cells RIPK3 in the AKI to CKD progression.
Methods
We evaluate the role of renal tubular epithelial cells RIPK3 through detecting its expression in renal puncture tissue and AKI to CKD progression animal model. The role of RIPK3 in promoting AKI-to-CKD transition and G2/M cell cycle arrest was evaluated using transgenic mice with specific knockout of proximal renal tubular epithelial cells RIPK3 or intervention of RIPK3 inhibitor GSK’872. Co-Immunoprecipitation and pull-down experiments were used to explore the interaction between the phosphorylated RIPK3 and CDK1. The mechanism that RIPK3 promote AKI to CKD transition through regulating G2/M cell cycle arrest were explored in vitro rescue experiments.
Results
Renal tubular epithelial cells RIPK3 was up-regulated in renal puncture tissues of CKD
patients after cardiac surgery-associated AKI and AKI to CKD progression animal models. GSK’872 intervention or specific knockout of proximal renal tubular epithelial cells RIPK3 could attenuate renal interstitial fibrosis and G2/M phase cell cycle arrest. Co-Immunoprecipitation and pull-down experiments confirmed that phosphorylated RIPK3 and CDK1 could bind directly. siRNA inhibiting the expression of CDK1 could attenuate the reno-protective effect of GSK'872 intervention or RIPK3 silence after intervention of TGF-β.
Conclusion
Renal tubular epithelial cells RIPK3 is up-regulated and activated during the AKI to CKD progression and drive the AKI progressing to CKD. The possible mechanism may be that RIPK3 can inhibit the activity of CDK1, and mediate the G2/M cell cycle arrest of renal tubular epithelial cell, which could provide a new theoretical and therapeutic target for delaying the AKI to CKD progression.