Arctigenin alleviates TGF-ß1-induced epithelial-mesenchymal transition and PAI-1 expression via AMPK/NF-κB pathway in peritoneal mesothelial cells.
Biochem Biophys Res Commun
; 520(2): 413-419, 2019 12 03.
Article
en En
| MEDLINE
| ID: mdl-31607474
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-ß1 (TGF-ß1)-induced EMT and the underlying mechanisms in HPMCs was investigated in this study. Firstly, the PD model was established by TGF-ß1 stimulation in cultured HPMCs in vitro, we found that TGF-ß1 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⯵M) ameliorated TGF-ß1-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-ß1-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-ß1 was reversely attenuated by Arc in HPMCs. However, the effect of Arc on TGF-ß1-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-ß1-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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Peritoneo
/
Inhibidor 1 de Activador Plasminogénico
/
Lignanos
/
Factor de Crecimiento Transformador beta1
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Transición Epitelial-Mesenquimal
/
Furanos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
China