Abstract: SA-PO420
C/EBPα Exacerbates Diabetic Nephropathy by Inducing ACSL4-Mediated Ferroptosis in Tubular Cells
Session Information
- Diabetic Kidney Disease: Basic - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Xia, Ziru, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- Gu, Xiangchen, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- Wang, Weiming, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
Group or Team Name
- Weiming Wang's Team.
Background
Diabetic nephropathy (DN) is a serious complication of diabetes, leading to the progressive decline of kidney function. In this study, we examined the increased expression of CCAAT/enhancer binding protein alpha (C/EBPα) in DN patients and investigated its potential role in DN pathogenesis.
Methods
Pepck-Cre+/Cebpa+/+ (WT) and Pepck-Cre+/Cebpafl/fl (KO) mice were streptozotocin (STZ)-induced for diabetes. Renal histopathology, UACR, BUN, SCr, and Cystatin C levels were assessed for renal injury. Kidney tissues were analyzed for ferroptosis markers (GPX4, 4-HNE, MDA). C/EBPα transcriptional activity was examined using CUT&TAG, dual-luciferase, and ChIP-qPCR.
Results
STZ-treated WT mice showed more severe pathological injury, elevated SCr, cystatin C, BUN, and UACR. They also displayed pronounced signs of ferroptosis, including increased MDA, 4-HNE, and reduced GPX4. We further demonstrated that C/EBPα attenuated renal ferroptosis by binding to the TRS of ACSL4, a key enzyme of lipid peroxidation.
Conclusion
We discovered that C/EBPα regulated ACSL4 expression by binding to its TRS, triggering lipid peroxidation and subsequent ferroptosis. And knockout of C/EBPα could alleviate ferroptosis and ameliorate tubular injuries in DN.
Funding
- Government Support – Non-U.S.