PhD Scientific Days 2022

Clinical Medicine VIII.

Effect of excess sodium chloride on the peritoneal fibrosis

Text of the abstract

Introduction: The most common contraindication of peritoneal dialysis is peritoneal fibrosis, which causes a decrease in peritoneal ultrafiltration. According to literature data, sodium accumulates in the peritoneal membrane as a result of high salt (NaCl) intake, leading to peritoneal fibrosis through osmotic effects, however, the underlying mechanisms are not fully elucidated.
Aims: We aimed to investigate the effect of a high salt environment on different peritoneal cell types and peritoneal tissue, with special reference to changes in fibroblast migration and gene expression associated with fibrosis.
Methods: The effects of high NaCl concentration and mannitol as osmotic control were investigated on the inflammation and fibrosis 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. The effect of a high salt environment on the migration of HPFs was also investigated.
Results: High salt concentrations decreased the level of the epithelial marker E-cadherin, while induced the expression of the mesenchymal marker α-SMA and SNAI1 in HPMCs, suggesting increased epithelial-mesenchymal transition due to salt loading. High NaCl environment resulted in increased profibrotic growth factor TGF-β, PDGF-B or CTGF expression both in HPMCs, HUVECs, and PBMCs. In addition, high salt concentration induced the expression of the inflammatory cytokine MCP-1 and IL-1β in HUVECs and/or PBMCs and the production of collagen in HPF cells. Our in vitro results were also supported by our ex vivo experiments on mouse peritoneum. Our results reveal the role of increased osmolarity on the gene expression changes described above. Furthermore, in cultured HPFs high salt concentration resulted in increased cell migration.
Conclusion: Based on our results, high salt environment and elevated osmolarity induce inflammation, the production of profibrotic growth factors, epithelial-mesenchymal transition, and peritoneal fibroblast migration, which processes lead to the development of fibrosis.
Támogatás: K125470; 20382-3/2018 FEKUTSTRAT; 2020-4.1.1-TKP2020; EFOP-3.6.3-VEKOP-16-2017-00009, STIA-KFI-2020 Semmelweis Tudományos Innovációs Alap.