期刊
KIDNEY RESEARCH AND CLINICAL PRACTICE
卷 38, 期 4, 页码 472-480出版社
KOREAN SOC NEPHROLOGY
DOI: 10.23876/j.krcp.19.049
关键词
Epithelial-mesenchymal transition; Fibrosis; Peritoneal dialysis; Peritoneum; Tranilast
资金
- Medical Research Center Program [2015R1A5A2009124]
- National Research Foundation of Korea - Ministry of Science, ICT, and Future Planning
Background: We investigated the effects of tranilast on epithelial-to-mesenchymal transition (EMT) in an animal model and on the EMT signaling pathway in human peritoneal mesothelial cells (HPMCs). Methods: We performed in vitro studies (cytotoxicity, cell morphology, and western blot analyses) on HPMCs from human omenta, along with in vivo studies (peritoneal membrane function and morphometric and immunohistochemical analyses) on Sprague Dawley rats. Thirty-two rats were divided into three groups: control (C) group (peritoneal dialysis [PD] catheter but not infused with dialysate), PD group (4.25% glucose-containing dialysate), and PD + tranilast group (4.25% glucose-containing dialysate along with tranilast). Results: In in vitro experiments, transforming growth factor-beta 1 (TGF-beta 1) increased a-smooth muscle actin and Snail expression and reduced E-cadherin expression in HPMCs. TGF-beta 1 also reduced cell contact, induced a fibroblastoid morphology, and increased phosphorylation of Akt, Smad2, and Smad3 in HPMCs. Tranilast significantly inhibited TGF-beta 1-induced EMT and attenuated these morphological changes in HPMCs. In in vivo studies, after 6 weeks of experimental PD, the peritoneal membrane was significantly thicker in the PD group than in the C group. Tranilast protected against PD-induced glucose mass transfer change and histopathological changes in rats. Conclusion: Tranilast prevented EMT both in HPMCs triggered with TGF-beta 1 and in rats with PD-induced peritoneal fibrosis. Thus, tranilast may be considered a therapeutic intervention that enables long-term PD by regulating TGF-beta 1 signaling pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据