Effects of tranilast on the epithelial-to-mesenchymal transition in peritoneal mesothelial cells
Seok Hui Kang1 , Sang Woon Kim2 , Keuk Jun Kim3 , Kyu Hyang Cho1 , Jong Won Park1 , Chan-Duck Kim4,* , Jun Young Do1,*
1Division of Nephrology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea
2Division of Gastro-Enterology, Department of Surgery, Yeungnam University Hospital, Daegu, Republic of Korea
3Department of Biomedical Laboratory Science, Daekyeung University, Gyeongsan, Republic of Korea
4Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
Correspondence to: Jun Young Do
Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea. E-mail: jydo@med.yu.ac.kr
Chan-Duck Kim
Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea. E-mail: drcdkim@knu.ac.kr
*Chan-Duck Kim and Jun Young Do contributed equally to this study.
Received: April 30, 2019; Revised: July 3, 2019; Accepted: July 9, 2019; Published online: September 25, 2019.
© The Korean Society of Nephrology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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-β1) increased α-smooth muscle actin and Snail expression and reduced E-cadherin expression in HPMCs. TGF-β1 also reduced cell contact, induced a fibroblastoid morphology, and increased phosphorylation of Akt, Smad2, and Smad3 in HPMCs. Tranilast significantly inhibited TGF-β1-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-β1 and in rats with PD-induced peritoneal fibrosis. Thus, tranilast may be considered a therapeutic intervention that enables long-term PD by regulating TGF-β1 signaling pathways.
Keywords: Epithelial-mesenchymal transition, Fibrosis, Peritoneal dialysis, Peritoneum, Tranilast


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