Abstract: TH-PO0658
Glucose-Derived Carbon Nanoparticles/Manganese (GCNPs/Mn) Ameliorate Experimental Myeloperoxidase (MPO)-ANCA-Associated Vasculitis by Attenuating Ferroptosis Through Enhancing Manganese Superoxide Dismutase (MnSOD) Activity
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Wang, Yiru, Ningbo No 2 Hospital, Ningbo, Zhejiang, China
- Luo, Qun, Ningbo No 2 Hospital, Ningbo, Zhejiang, China
- Zhou, Fangfang, Ningbo No 2 Hospital, Ningbo, Zhejiang, China
Background
This study clarifies NETs-induced endothelial injury mechanisms and investigates GCNPs/Mn for ANCA-associated vasculitis (AAV) treatment.
Methods
We measured markers (oxidative stress, ferroptosis proteins etc.) to clarify ferroptosis in NETs-induced endothelial injury and GCNPs/Mn's effects. RNA sequencing and MnSOD siRNA explored its mechanism. In vivo, AAV models were established in WKY rats via MPO or PTU to evaluate the renal injury.
Results
In vitro tests showed NETs caused endothelial injury, mitochondrial dysfunction, oxidative stress, and ferroptosis-related changes (Fig 1A-E). GCNPs/Mn inhibited NETs-induced ferroptosis and injury (Fig 1F), restoring MnSOD activity (Fig 1G). Confocal and ICP-MS revealed GCNPs/Mn released Mn ions in lysosomes (Fig 1H). MnSOD siRNA blocked GCNPs/Mns protective effects (Fig 1I-J). Transcriptomics linked its action to NF-κB (Fig 1K), confirmed by protein assays (Fig 1L-M). In animal models, GCNPs/Mn reduced renal ferroptosis, injury, and proteinuria, restoring function (Fig 2).
Conclusion
GCNPs/Mn alleviates endothelial cell injury related to ferroptosis induced by NETs by regulating the MnSOD/NF-κB signaling pathway, providing new insights into AAV pathogenesis and potential therapeutic strategies.