Effect of the protease inhibitor MG132 on the transforming growth factor-β/Smad signaling pathway in HSC-T6 cells.
10.1007/s11596-013-1149-0
- Author:
Zhang-peng REN
1
;
Li-ping SUN
;
You-chen XIA
;
Qiao-xia TONG
Author Information
1. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, rzp2009@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Leupeptins;
pharmacology;
Protease Inhibitors;
pharmacology;
Rats;
Signal Transduction;
drug effects;
Smad Proteins;
metabolism;
Transforming Growth Factor beta;
metabolism
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(4):501-504
- CountryChina
- Language:English
-
Abstract:
The activation of hepatic stellate cells (HSCs) and their transformation to myofibroblasts are the key steps in the pathological progress of liver fibrosis. The transforming growth factor-β (TGFβ)/Smad pathway is involved in the proliferation and collagen synthesis of HSCs. This study aimed to examine the effect of the protease inhibitor MG132 on the signaling pathway of TGFβ/Smad in HSC-T6 cells and seek a novel therapeutic approach for liver fibrosis. The HSC-T6 cells were treated with MG132 at different concentrations (0-10 μmol/L). Cell proliferation was detected by MTT method. The mRNA and protein expression levels of TGFβ1, Smad3 and Smad7 were determined in HSC-T6 cells by real-time PCR and Western blotting, respectively, after treatment with MG132 at different concentrations (1, 2, 3 μmol/L) or RPMI1640 alone (serving as control). The results showed that MG132 could inhibit the proliferation of HSC-T6 cells in a dose-dependent manner, and the IC(50) of MG132 was 6.84 μmol/L. After treatment with MG132 at 1, 2 or 3 μmol/L for 24 h, the mRNA expression levels of TGF-β1 and Smad3 were significantly decreased (P<0.05), but the Smad7 mRNA expression had no significant change (P>0.05). There was also a significant decrease in the protein expression level of TGF-β1 and Smad3 (P<0.05). However, the expression of Smad7 protein was substantially increased when compared with the control group (P<0.05). It was concluded that the inhibition of TGFβ/Smad pathway in HSC-T6 cells by MG132 can reduce the production of profibrosis factors (TGFβ1, Smad3) and promote the expression of anti-fibrosis factor (Smad7), suggesting that MG132 may become a potential therapeutic alternative for liver fibrosis.
