PhD Scientific Days 2021

CL_IV_L: Clinical Medicine IV. Lectures

Excess Sodium Chloride Induces Inflammation and Profibrotic Response in Peritoneal Cells

Text of the abstract

Introduction: Peritoneal scarring leads to decreased peritoneal ultrafiltration capacity which is the main cause of technical failure in peritoneal dialysis patients. High dietary salt intake (NaCl) was reported to induce peritoneal fibrosis due to accumulation of sodium in the peritoneal membrane, however, the underlying mechanisms are not clear.
Aims: Our aim was to investigate the effect of high salt environment on the pathomechanism of peritoneal fibrosis.
Methods: The effect of high NaCl concentrations and mannitol as osmotic control was investigated in vitro on the changes of inflammation and fibrosis related gene expression in human primary mesothelial cells (HPMC), human primary peritoneal fibroblasts (HPF), human endothelial cells (HUVEC) and human peripheral immune cells (PBMC), respectively. The ex vivo effect of high salt loading was also investigated on peritoneal tissue samples of mice.
Results: High salt loading induced epithelial-mesenchymal transition in HPMCs evidenced by decreased epithelial marker E-cadherin and increased mesenchymal marker α-SMA and SNAI1 expressions. Increased salt environment also resulted in elevated profibrotic growth factor TGF-ß, PDGF-B or CTGF expression in HPMCs, HUVECs and PBMCs. In addition, high salt induced the MCP-1 and IL-1β expression of HUVECs and/or PBMCs. Increased salt concentration induced the collagen production of HPFs. In line with the in vitro results the ex vivo experiments also demonstrated that high salt environment increased the expression of α-SMA, SNAI1, TGF-ß, CTGF and IL-1β in peritoneal tissue samples. Furthermore, our in vitro and ex vivo results also demonstrated the role of increased osmolarity on the detected gene expression changes.
Conclusion: Our results demonstrated that the high dietary salt intake and the consequently increased peritoneal sodium concentration induces profibrotic changes in peritoneal cells responsible for integrity and ultrafiltration capacity of peritoneal membrane.
Funding: This study was supported by grant K125470, EFOP-3.6.3-VEKOP-16-2017-00009, 20382-3/2018 FEKUTSTRAT, 2020-4.1.1- TKP2020 and STIA-KFI-2020.

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine