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Arctigenin alleviates TGF-β1-induced epithelial-mesenchymal transition and PAI-1 expression via AMPK/NF-κB pathway in peritoneal mesothelial cells.

Authors
  • Jin, Gang1
  • Su, Yanjin2
  • Dong, Qianlan3
  • Zhao, Xiaohong3
  • Zhang, Linping4
  • Yan, Xiaohui5
  • 1 Center of Kidney Dialysis, The Shaanxi Provincial People's Hospital, Xi'an, 710068, China; Shaanxi University of Chinese Medicine, Xi'an, 712046, China. , (China)
  • 2 Shaanxi University of Chinese Medicine, Xi'an, 712046, China. , (China)
  • 3 Center of Kidney Dialysis, The Shaanxi Provincial People's Hospital, Xi'an, 710068, China. , (China)
  • 4 Center of Kidney Dialysis, The Shaanxi Provincial People's Hospital, Xi'an, 710068, China. Electronic address: [email protected] , (China)
  • 5 Center of Kidney Dialysis, The Shaanxi Provincial People's Hospital, Xi'an, 710068, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Dec 03, 2019
Volume
520
Issue
2
Pages
413–419
Identifiers
DOI: 10.1016/j.bbrc.2019.09.130
PMID: 31607474
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Peritoneal fibrosis (PF) caused by long-term peritoneal dialysis is closely associated with the epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs). Moreover, the anti-fibrotic role of Arctigenin (Arc) has been reported in several fibrosis disorders. Therefore, the preventive effect of Arc on transforming growth factor-β1 (TGF-β1)-induced EMT and the underlying mechanisms in HPMCs was investigated in this study. Firstly, the PD model was established by TGF-β1 stimulation in cultured HPMCs in vitro, we found that TGF-β1 significantly increased the EMT markers (α-SMA, vimentin, and fibronectin) and plasminogen activator inhibitor type 1 (PAI-1) expressions, but decreased epithelial marker (E-cadherin). Co-treatment with Arc (10, 20, 40 μM) ameliorated TGF-β1-induced EMT in a dose-dependent manner, and the expression of PAI-1 was also inhibited by Arc, which was abrogated by restoration of PAI-1. Moreover, Arc enhanced the phosphorylated AMP-activated protein kinase (AMPK), but inhibited the phosphorylated IκBα level and nuclear translocation of nuclear factor κB (NF-κB) p65 in TGF-β1-induced HPMCs. ChIP and Luciferase reporter assays verified that the increased binding capacity of NF-κB to the promoter of PAI-1 induced by TGF-β1 was reversely attenuated by Arc in HPMCs. However, the effect of Arc on TGF-β1-induced NF-κB activation, PAI-1 expression and EMT in HPMCs was attenuated by AMPK agonist Compound C. In conclusion, these data demonstrated that Arc suppressed TGF-β1-induced EMT by activating the AMPK/NF-κB pathway to inhibit PAI-1 expression in HPMCs. Therefore, Arc might act as a potential therapeutic agent for PD treatment. Copyright © 2019 Elsevier Inc. All rights reserved.

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