Abstract: SA-PO0167
BTB and CNC Homology 1 Deficiency Mitigates Ischemia-Reperfusion-Induced AKI in a Glutaredoxin-2-Dependent Manner
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Li, Jun, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
- Zhang, Hui, Jiangnan University Wuxi School of Medicine, Wuxi, Jiangsu, China
- Ke, Qi, Jiangnan University Wuxi School of Medicine, Wuxi, Jiangsu, China
- Lu, Jingyao, Jiangnan University Wuxi School of Medicine, Wuxi, Jiangsu, China
Background
The BTB and CNC homology 1 (Bach1) binds to antioxidant response elements (ARE) in the promoter regions of target genes, thereby suppressing the transcription of antioxidant genes. Glutaredoxin-2 (Grx2) is essential for maintaining mitochondrial function under oxidative stress conditions. However, the protective effects and underlying mechanisms of Bach1/Grx2 axis against renal ischemia-reperfusion (I/R) injury remain poorly understood.
Methods
Renal I/R model was established using C57BL/6J wild-type mice and BACH1 knockout mice (Bach1-/-), respectively. HK-2 cells (human proximal tubular cells strain) were transfected with Grx2-siRNA plasmid, Grx2-overexpression (Grx2-OE) plasmid and Bach1-siRNA plasmid, respectively. The regulating effect of Bach1 on Grx2 was confirmed by the luciferase reporter gene and electrophoretic mobility shift assay (EMSA).
Results
BACH1 was prominently upregulated while Grx2 was significantly downregulated in the renal proximal tubules of the renal I/R injury mice models and patients with acute tubular necrosis. Overexpression of Grx2 alleviated mitochondrial dysfunction while Grx2 siRNA aggravated mitochondrial dysfunction in HK-2 cells following H/R injury. Bach1 deletion upregulated the expression of Grx2, decreased oxidative stress and improved mitochondrial function in I/R-induced renal proximal tubular injury models in vivo and in vitro. Luciferase reporter gene detection and EMSA confirmed that the Bach1 can specifically bind to the promoter region of Grx2.
Conclusion
Bach1/ glutaredoxin-2 pathway induced the oxidative stress and mitochondrial dysfunction of acute renal ischemia/reperfusion. Therefore, targeting Bach1 may be a promising intervention strategy for ischemia/reperfusion-induced acute kidney injury.
Funding
- Government Support – Non-U.S.