Kidney Res Clin Pract.
2019 Dec;38(4):472-480. 10.23876/j.krcp.19.049.
Effects of tranilast on the epithelial-to-mesenchymal transition in peritoneal mesothelial cells
- Affiliations
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- 1Division of Nephrology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea. jydo@med.yu.ac.kr
- 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. drcdkim@knu.ac.kr
- KMID: 2469377
- DOI: http://doi.org/10.23876/j.krcp.19.049
Abstract
- 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.
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