Rhein inhibits transforming growth factor beta1 induced plasminogen activator inhibitor-1 in endothelial cells.
- Author:
Jiaming ZHU
1
;
Zhihong LIU
;
Haidong HUANG
;
Zhaohong CHEN
;
Leishi LI
Author Information
- Publication Type:Journal Article
- MeSH: Anthraquinones; pharmacology; Cells, Cultured; Dose-Response Relationship, Drug; Endothelium, Vascular; drug effects; metabolism; Humans; Mitogen-Activated Protein Kinase 1; metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; metabolism; Plasminogen Activator Inhibitor 1; biosynthesis; genetics; RNA, Messenger; analysis; Transforming Growth Factor beta; antagonists & inhibitors; Transforming Growth Factor beta1
- From: Chinese Medical Journal 2003;116(3):354-359
- CountryChina
- Language:English
-
Abstract:
OBJECTIVESTo investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor beta1 (TGFbeta1), and to explore the mechanism of the protective action of rhein on endothelial cells.
METHODSA human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 was determined by immunoprecipitation analysis and western blot.
RESULTSTGFbeta1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFbeta1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFbeta1 in human endothelial cells.
CONCLUSIONSOur results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.
