Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
Sci Rep. 2018 Apr 12;8(1):5863. doi: 10.1038/s41598-018-21807-x.
Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (HS) 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 HS 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 HS improves PS by inhibiting EMT in MCs. The anti-EMT effect of HS is associated with the inhibition of inflammation and TGF-β1-Smad signal pathway.
腹膜纤维化（PS）决定了腹膜透析（PD）的长期预后。我们之前证实了硫化氢（HS）抑制 PS，但它的细胞机制尚未完全阐明。间皮细胞（MCs）的上皮-间充质转化（EMT）是 PS 的一个重要细胞事件，因此我们研究了 HS 是否可以影响 MCs 中的 EMT。用 4.25%葡萄糖 PD 液加脂多糖处理大鼠 28 天以产生 PS，并同时给予 NaHS（56μg/kg.d）。与 PS 组相比，NaHS（56μg/kg.d）减少了亚膜下区胶原的沉积。在原代培养的大鼠 MCs 中，4.25%葡萄糖 PD 液诱导 MCs 的 EMT，表现为 ZO-1 和 Cytokeratin 的丢失，以及α-SMA、纤溶酶原激活物抑制剂 1、纤维连接蛋白和 TGF-β1 蛋白的增加。PD 液还增加了 IL-6 和单核细胞趋化蛋白-1 mRNA 的表达以及 Smad2/3 和 Smad3 的磷酸化。HS（50-300μmol/L）以 100μmol/L 的最佳剂量逆转了上述变化。因此，外源性 HS 通过抑制 MCs 中的 EMT 来改善 PS。HS 的抗 EMT 作用与抑制炎症和 TGF-β1-Smad 信号通路有关。
