Abstract: FR-PO182
Proximal Tubule-Specific Knockout of G3bp1 Enhances Kidney Injury after Cisplatin Administration and Kidney Ischemia-Reperfusion
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wang, Shixuan, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Dong, Zheng, Augusta University Medical College of Georgia, Augusta, Georgia, United States
Background
Stress granule, mainly containing RNA-binding proteins (RBPs) and RNAs, is one type of cytoplasmic membraneless structure formed upon stress in eukaryotic cells. G3bp1 is a core protein in stress granule. The role of G3bp1 and associated stress granules in renal pathophysiology is largely unknown.
Methods
To study the function of stress granule and G3bp1 in the kidney, we established a kidney proximal tubule-specific G3bp1 knockout (PT-G3bp1-KO) mouse model by crossing G3bp1-floxed mice with PEPCK-Cre mice. PT-G3bp1-KO mice and their wild-type (WT) littermates were subjected to cisplatin nephrotoxicity or renal ischemia/reperfusion to induce acute kidney injury.
Results
Compared with WT mice, PT-G3bp1-KO mice had more severe kidney injury after cisplatin or ischemia/reperfusion treatment in histological analysis. Consistently, KO mice showed significantly higher levels of serum creatinine after AKI challenge. By TUNEL staining, more apoptotic cells were found in KO mice than in the wild-type. Immunoblotting also detected higher level of caspase-3 cleavage or activation in KO mice kidneys than in wild-type tissues. Additionally, more Ki-67-positive cells were found in KO mice kidney tissues than in the wild-type.
Conclusion
Our data indicate that G3bp1 and associated stress granules play a protective role in proximal tubule cells during acute kidney injury, suggesting a new strategy for the prevention and treatment of this devastating renal diseases.
Funding
- NIDDK Support