Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells
We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal f...
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doaj-83268656d7264a2ba8b0cd6ada015efc2021-04-29T23:06:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01224739473910.3390/ijms22094739Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial CellsYunmee Lho0Jun-Young Do1Jung-Yoon Heo2A-Young Kim3Sang-Woon Kim4Seok-Hui Kang5Department of Internal Medicine, Smart-Aging Convergence Research Center, College of Medicine Yeungnam University, Daegu 42415, KoreaDivision of Nephrology, Department of Internal Medicine, College of Medicine Yeungnam University, Daegu 42415, KoreaDepartment of Internal Medicine, Smart-Aging Convergence Research Center, College of Medicine Yeungnam University, Daegu 42415, KoreaDivision of Nephrology, Department of Internal Medicine, College of Medicine Yeungnam University, Daegu 42415, KoreaDivision of Gastro-Enterology, Department of Surgery, College of Medicine Yeungnam University, Daegu 42415, KoreaDivision of Nephrology, Department of Internal Medicine, College of Medicine Yeungnam University, Daegu 42415, KoreaWe investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.https://www.mdpi.com/1422-0067/22/9/4739peritoneal fibrosisperitoneal dialysisSmad activationtransforming growth factor-beta 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yunmee Lho Jun-Young Do Jung-Yoon Heo A-Young Kim Sang-Woon Kim Seok-Hui Kang |
spellingShingle |
Yunmee Lho Jun-Young Do Jung-Yoon Heo A-Young Kim Sang-Woon Kim Seok-Hui Kang Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells International Journal of Molecular Sciences peritoneal fibrosis peritoneal dialysis Smad activation transforming growth factor-beta 1 |
author_facet |
Yunmee Lho Jun-Young Do Jung-Yoon Heo A-Young Kim Sang-Woon Kim Seok-Hui Kang |
author_sort |
Yunmee Lho |
title |
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells |
title_short |
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells |
title_full |
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells |
title_fullStr |
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells |
title_full_unstemmed |
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells |
title_sort |
effects of tgf-β1 receptor inhibitor gw788388 on the epithelial to mesenchymal transition of peritoneal mesothelial cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model. |
topic |
peritoneal fibrosis peritoneal dialysis Smad activation transforming growth factor-beta 1 |
url |
https://www.mdpi.com/1422-0067/22/9/4739 |
work_keys_str_mv |
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1721500097414430720 |