Abstract: SA-PO0417
Targeting Macrophage Extracellular Traps to Disrupt Encapsulating Peritoneal Sclerosis Formation
Session Information
- Home Dialysis: Science and Cases, from Lab to Living Room
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 802 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Sun, Yuxiang, The Third Affiliated Hospital of Sun Yet-sun University Department of Nephrology, Guangzhou, Guangdong, China
- Sun, Juan, The Third Affiliated Hospital of Sun Yet-sun University Department of Nephrology, Guangzhou, Guangdong, China
- Zhou, Hu, The Third Affiliated Hospital of Sun Yet-sun University Department of Nephrology, Guangzhou, Guangdong, China
- Peng, Hui, The Third Affiliated Hospital of Sun Yet-sun University Department of Nephrology, Guangzhou, Guangdong, China
Background
As the most serious complication of peritoneal dialysis, encapsulating peritoneal sclerosis (EPS) poses a significant threat to the life safety of peritoneal dialysis patients. However, the mechanism of peritoneum adhesion formation in EPS remains unclear. This study aims to dissect the peritoneal environment characteristics of EPS at the single-cell level, and explore the mechanism of EPS.
Methods
Peritoneums of EPS patients were collected for scRNA-seq, 10x visuim spatial sequencing, electron microscopy and immunofluorescence were used to identify macrophage extracellular traps (METs), gene knockout and drug intervention were conducted to verify the pathogenic role of METs, then fluorescent tracking was utilized to observe the "netting" function of METs, and primary fibroblasts stimulated by METs were collected for RNA-seq to explore the mechanism of METs-induced fibroblast activation.
Results
Spatial and scRNA-seq analysis revealed a remarkable increase of macrophages and myofibroblasts infiltrations in EPS peritoneum, and their interaction increased. Pro-inflammatory macrophages amplified in EPS group, and this subtype enriched in the extracellular trap formation pathway. The concentration of METs correlated with EPS severity, while gene knockout of PAD4 and treatment of DNase I significantly ameliorated METs formation, reducing adhesions. Mechanistically, cells adhered to the METs and aggregate into clusters. METs also induce fibroblast activation through ILK/Rac1 and p38/MAPK pathway, promoting and peritoneal adhesion.
Conclusion
METs contribute to the progression of EPS by promoting fibroblast activation via ILK/Rac1 and p38/MAPK pathway and serving as scaffolds for cell aggregation, thus enhancing peritoneal thickening and adhesion. Targeting METs may offer a novel therapeutic strategy for EPS.