Abstract: FR-PO0164
Neutrophil Extracellular Traps (NETs) Mediate Ferroptosis in Contrast-Induced AKI by Releasing IL-33
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Ma, Mengqing, Nanjing First Hospital, Nanjing, Jiangsu, China
- Hao, Zhang, Nanjing First Hospital, Nanjing, Jiangsu, China
- Wan, Xin, Nanjing First Hospital, Nanjing, Jiangsu, China
- Cao, Changchun, Sir Run Run Hospital Nanjing Medical University, Nanjing, Jiangsu, China
Background
The pathogenesis of contrast-induced acute kidney injury (CIAKI) is complex and there is still a lack of effective intervention targets. The exploration of its mechanism is crucial. In recent years, the role of neutrophil extracellular traps in kidney disease has gradually received attention, but its relationship with the occurrence of CIAKI is still unclear.
Methods
Blood samples from patients with CIAKI were collected to detect the expression of NETs and IL33. At the same time, single-cell sequencing and gene knockout mice were used to verify the expression of NETs,IL33 and ferroptosis-related indicators in the kidneys of CIAKI mice. In the cell experiment, contrast agents were used to directly stimulate Neu to form NETs,and HK2 cells were co-cultured with renal tubular epithelial cells (HK2) to detect the expression of HK2 cell apoptosis and ferroptosis-related proteins. GSEA analysis was performed on the pathways related to AKI with high and low expression of IL33 in the transcriptome sequencing data of CIAKI mice, and the pathways related to IL-33 when AKI occurred were found.
Results
The results of single-cell sequencing of CIAKI mice showed that the expression of NETs-related genes increased in neutrophils with high expression of IL33. At the clinical level, among 280 patients who underwent CAG examination, the levels of MPO, NE and IL-33 in the serum of CIAKI patients were significantly increased. At the animal level, NETs and ferroptosis are involved in the occurrence of CIAKI and mainly cause tubular damage. At the cellular level, the use of contrast agents can directly induce Neu to form NETs,while IL-33 participates in the formation of NETs and promotes ferroptosis of tubular epithelial cells. After NETs damage HK2 cells, the IKKα/β-catenin pathway is activated to participate in kidney repair. After knocking down IL-33, the inhibitory effect of IKKα/β-catenin on ACSL4 is enhanced. The results of IF and IP further show that IKKα and β-catenin have an interactive relationship, which can promote β-catenin to enter the nucleus and exert an inhibitory effect on ACSL4.
Conclusion
NETs participate in the occurrence of CIAKI by mediating ferroptosis of renal tubular epithelial cells through IL-33, while activated IKKα/β-catenin can inhibit the expression of ACSL4 and participate in renal repair during CIAKI.