PhD Scientific Days 2023

Budapest, 22-23 June 2023

Molecular Sciences - Posters K

Role of High Salt Intake in the Pathomechanism of Peritoneal Fibrosis

Domonkos Pap 1,2, Csenge Pajtók 1, Apor Veres-Székely 1,2, Beáta Szebeni 1,2, Csenge Szász 1, Péter Bokrossy 1, Tivadar Tulassay 1,2, Ádám Vannay 1,2, Attila J. Szabó 1,2

1 Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest, Hungary
2 ELKH-SE Pediatrics and Nephrology Research Group, Budapest, Hungary

Text of the abstract

Introduction: The most common contraindication of peritoneal dialysis is peritoneal fibrosis (PF), leading to a decline in dialytic capacity and ultimately PD technique failure. According to literature data, sodium (Na+) accumulates in the peritoneal wall as a result of high salt (NaCl) intake, leading to peritoneal fibrosis, however, the underlying mechanisms are not fully understood. In the present study, our goal was to reveal how the increasing sodium content induces an inflammatory and profibrotic response in the main effector cells of PF.

Aim: In the present study, we aimed to reveal how the increasing sodium content induces an inflammatory and profibrotic response in the main effector cells of PF.

Methods: The effects of increased NaCl concentrations and mannitol as an osmotic control were investigated on the changes of inflammation, fibrosis, and epithelial-mesenchymal transition (EMT) related gene expression in vitro on human primary mesothelial cells (HPMC), human primary peritoneal fibroblasts (HPF), endothelial cells (HUVEC), immune cells (PBMC), as well as ex vivo on mouse peritoneal tissue samples.

Results: Our in vitro and ex vivo data showed that a high salt environment resulted in increased production of inflammatory cytokines and profibrotic growth factors, including IL-1ß, IL-6, MCP-1, TGF-ß, PDGF-B, and CTGF in HPMCs, HUVECs or PBMCs, and in ex vivo peritoneal samples. We also demonstrated that high salt induces EMT by increasing the expression of mesenchymal marker α-SMA and SNAI1 in HPMCs, HUVECs, and peritoneal tissue samples. Furthermore, high salt loading resulted in both increased extracellular matrix production in HPF and ex vivo tissue samples. In addition, our results revealed the role of increased osmolarity on the gene expression changes described above.

Conclusion: Our results demonstrate that Na+ excess induces a profibrotic response in the main effector cells of peritoneal fibrosis. Furthermore, draw attention to that excessive salt intake is a potential risk factor for patients on peritoneal dialysis.

Funding: This research was funded by National Research, Development and Innovation Office (NKFIH) K-142728; Semmelweis University, TKP2021-EGA-24, STIA-KFI-2021; Eötvös Loránd Research Network, ELKH-POC-2022-024; New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund, ÚNKP-22-4-II-SE-12, ÚNKP-22-5-SE-17; János Bolyai Research Scholarship by Hungarian Academic of Sciences

E-mail: pap.domonkos@med.semmelweis-univ.hu
Institute: Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest, Hungary