Pediatric Center, MTA Center of Excellence, Semmelweis University, 1085 Budapest, Hungary.
HUN-REN-SU Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary.
Int J Mol Sci. 2023 Sep 6;24(18):13765. doi: 10.3390/ijms241813765.
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 , , , , , and both in vitro and ex vivo. We also demonstrated that high salt induces mesenchymal transition by decreasing the expression of epithelial marker and increasing the expression of mesenchymal marker and 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.
最近的研究引起了人们的关注，即过量的盐（NaCl）摄入如何通过钠积累和渗透事件引起腹膜的纤维化改变。我们的研究旨在更好地了解潜在的机制。研究了额外的 NaCl 对人原代间皮细胞（HPMC）、人原代腹膜成纤维细胞（HPF）、内皮细胞（HUVEC）、免疫细胞（PBMC）以及腹膜组织样本的体外和体内的影响。我们的结果表明，高盐环境和随之而来的渗透压增加会增加炎症细胞因子、促纤维化生长因子和肾素-血管紧张素-醛固酮系统的成分的产生，包括 、 、 、 、 、 和 ，无论是在体外还是体内。我们还证明，高盐通过降低上皮标记物 的表达和增加间充质标记物 的表达，诱导 HPMCs、HUVECs 和腹膜样本中的间充质转化。此外，高盐增加了 HPFs 细胞外基质的产生。我们证明，过量的 Na 和随之而来的渗透压增加会在腹膜细胞中诱导全面的促纤维化反应，从而促进腹膜纤维化的发展。
