Abstract: SA-PO0421
STING-Mediated Cytosolic DNA Sensing as a Novel Mechanism of Peritoneal Damage: Evidence from Transcriptomic and Functional Studies
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
- Marchant, Vanessa A, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- Tejedor, Lucia, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- Battaglia-Vieni, Antonio, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- Salguero, Elena Flores, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- Milhano Santos, Fátima, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- García Caballero, Cristina, Inflammation and Immunopathology of Organs and Systems. University Hospital La Princesa, Madrid, Spain
- Rayego-Mateos, Sandra, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
- Ramos Ruiz, Ricardo, IMDEA Food Institute, Universidad Autónoma de Madrid, Madrid, Spain
- Sandoval, Pilar, Tissue and Organ Homeostasis Program, Centro de Biología Molecular Severo Ochoa (CBM), CSIC - Universidad Autónoma de Madrid, Madrid, Spain
- Lopez-Cabrera, Manuel, Tissue and Organ Homeostasis Program, Centro de Biología Molecular Severo Ochoa (CBM), CSIC - Universidad Autónoma de Madrid, Madrid, Spain
- Bajo, Maria A., Inflammation and Immunopathology of Organs and Systems. University Hospital La Princesa, Madrid, Spain
- Ramos, Adrian Mario, Laboratory of Nephrology and Hypertension, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM),, Madrid, Spain
- Ruiz-Ortega, Marta, Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Background
Peritoneal dialysis (PD) is a widely used kidney replacement therapy. Nevertheless, long-term exposure to PD fluids and peritonitis episodes can result in peritoneal membrane (PM) damage, leading to ultrafiltration failure. Therefore, therapies aiming to preserve PM functionality are crucial. In this work, we aimed to unravel novel molecular mechanisms driving peritoneal injury through a transcriptomic approach.
Methods
Different mouse models of peritoneal damage were done: a model of peritoneal exposure to 0.1% chlorhexidine gluconate (CHX), a S. epidermidis-induced peritonitis model, and a post-surgical intra-abdominal adhesion model. Peritoneal tissue from the 10-day CHX model was subjected to bulk RNA-sequencing and functional enrichment analyses. Functional relevance of STING was evaluated in STING-deficient mice (STING-KO) and wild-type (WT) mice treated with the STING inhibitor C-176.
Results
Transcriptomic profiling identified 1,050 differentially expressed genes (974 upregulated and 76 downregulated). Functional enrichment analyses revealed multiple innate immune pathways, among which the cytosolic DNA-sensing pathway emerged as a novel mechanism not described for this pathology. Activation of this pathway was evidenced by the upregulation of STING and downstream effectors such as TBK1, IRF3, NF-κB, and ISGs. After CHX exposure, STING-KO mice exhibited reduced peritoneal thickening, fibrosis, immune cell infiltration, and inflammatory gene expression compared to WT mice. Pharmacological inhibition of STING with C-176 replicated these protective effects, attenuating NF-κB activation and restoring inflammatory markers. Additionally, STING deficiency reduced peritoneal inflammation in bacterial peritonitis and decreased adhesion scores in the post-surgical adhesion model. Moreover, STING overexpression was observed in human peritoneal biopsies from PD patients, highlighting its clinical relevance.
Conclusion
This study identifies the STING-mediated cytosolic DNA-sensing pathway as a novel pathogenic mechanism in peritoneal damage and proposes STING as a potential therapeutic target in PD-related peritoneal injury.
Funding
- Government Support – Non-U.S.