Role of PPAR-γ-regulated autophagy in genistein-induced inhibition of hepatic stellate cell activation.
10.12122/j.issn.1673-4254.2019.05.10
- Author:
Xipeng LIU
1
;
Meifang ZHANG
1
;
Haifeng ZHANG
1
;
Anda ZHAO
1
;
Juan SUN
1
;
Wen TANG
1
Author Information
1. Department of Clinical Nutrition, Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
- Publication Type:Journal Article
- Keywords:
PPAR-γ;
autophagy;
genistein;
hepatic stellate cells
- MeSH:
Anticarcinogenic Agents;
pharmacology;
Autophagy;
Collagen Type I;
Genistein;
pharmacology;
Hepatic Stellate Cells;
Humans;
PPAR gamma;
physiology
- From:
Journal of Southern Medical University
2019;39(5):561-565
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect.
METHODS:Cultured HSC-T6 cells were exposed to different concentrations of genistein for 48 h, and HSC activation was verified by detecting the expressions of -SMA and 1(I) collagen; autophagy activation in the cells was determined by detecting the expressions of LC3-II and p62 using Western blotting. The autophagy inhibitor 3-MA was used to confirm the role of autophagy in genistein-induced inhibition of HSC activation. A PPAR-γ inhibitor was used to explore the role of PPAR-γ in activating autophagy in the HSCs.
RESULTS:Genistein at concentrations of 5 and 50 μmol/L significantly inhibited the expressions of -SMA and 1(I) collagen ( < 0.05), markedly upregulated the expressions of PPAR-γ and the autophagy-related protein LC3-II ( < 0.05) and significantly down-regulated the expression of the ubiqutin-binding protein p62 ( < 0.05) in HSC-T6 cells. The cells pretreated with 3-MA prior to genistein treatment showed significantly increased protein expressions of -SMA and 1(I) collagen compared with the cells treated with genistein only ( < 0.05). Treatment with the PPAR-γ inhibitor obviously lowered the expression of LC3-II and enhanced the expression p62 in genistein-treated HSC-T6 cells, suggesting the activation of the autophagy pathway.
CONCLUSIONS:PPAR-γ- regulated autophagy plays an important role in mediating genistein-induced inhibition of HSC activation .
