Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells

Shengnan Cheng,Luyan Gao,Yuanyuan Li,Kai Song,Ying Lu,Huaying Shen

doi:10.1038/s41598-018-21807-x

Abstract

Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we therefore investigated whether EMT can be affected by H2S in MCs. Rats were treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to produce PS, and NaHS (56 μg/kg.d) was given simultaneously. NaHS (56 μg/kg.d) reduced the deposition of collagen in the submesothelial zone compared with the PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in MCs featured as loss of ZO-1 and Cytokeratin, and increase of α-SMA, plasminogen activator inhibitor 1, fibronectin and TGF-β1 proteins. PD fluid also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well as the phosphorylation of Smad2/3 and Smad3. NaHS (50–300 μmol/L) reversed the above alterations with the optimal dose at 100 μmol/L. Thus, exogenous H2S improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated with the inhibition of inflammation and TGF-β1-Smad signal pathway.

Highlights

Peritoneal fibrosis induced by the chronic stimulation of high glucose peritoneal dialysis fluid and frequent peritonitis is a major cause of ultrafiltration failure of peritoneal dialysis (PD)[1]
The present study demonstrated that high glucose peritoneal solution induced epithelial-mesenchymal transition (EMT) in primarily cultured peritoneal mesothelial cells
To the best of our knowledge, this is the first work to confirm the inhibitory effect of EMT of H2S in peritoneal mesothelial cells

Summary

Introduction

Peritoneal fibrosis induced by the chronic stimulation of high glucose peritoneal dialysis fluid and frequent peritonitis is a major cause of ultrafiltration failure of peritoneal dialysis (PD)[1]. The pathological characteristic of peritoneal fibrosis consists of the loss of mesothelial cells (MCs), neovascularization, thickened submesothelial zone and the presence of myofibroblasts[2]. Interventions against these histological features are believed to ameliorate peritoneal fibrosis and improve the long term outcome of PD patients. For the last twenty years, epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells has been used to explain the loss of MCs and the occurrence of myofibroblasts during peritoneal fibrosis[6]. We examined the effect of H2S on EMT induced by 4.25% peritoneal dialysis fluid in primarily cultured rat MCs. The potential mechanisms of the anti-EMT effect of H2S were explored

Methods

Results

Conclusion