Recent studies draw attention to how excessive salt (NaCl) intake induces fibrotic
alterations in the peritoneum through sodium accumulation and osmotic events. The
aim of our study was to better understand the underlying mechanisms. The effects of
additional NaCl were investigated on human primary mesothelial cells (HPMC), human
primary peritoneal fibroblasts (HPF), endothelial cells (HUVEC), immune cells (PBMC),
as well as ex vivo on peritoneal tissue samples. Our results showed that a high-salt
environment and the consequently increased osmolarity increase the production of inflammatory
cytokines, profibrotic growth factors, and components of the renin–angiotensin–aldosterone
system, including IL1B, IL6, MCP1, TGFB1, PDGFB, CTGF, Renin and Ace both in vitro
and ex vivo. We also demonstrated that high salt induces mesenchymal transition by
decreasing the expression of epithelial marker CDH1 and increasing the expression
of mesenchymal marker ACTA2 and SNAIL1 in HPMCs, HUVECs and peritoneal samples. Furthermore,
high salt increased extracellular matrix production in HPFs. We demonstrated that
excess Na+ and the consequently increased osmolarity induce a comprehensive profibrotic
response in the peritoneal cells, thereby facilitating the development of peritoneal
fibrosis.
