1. Inhibition of transforming growth factor-β-induced liver fibrosis by a retinoic acid derivative via the suppression of Col 1A2 promoter activity
- Author
-
Yang, Kun-Lin, Chang, Wen-Teng, Hung, Kuo-Chen, Li, Eric I.C., and Chuang, Chia-Chang
- Subjects
- *
GROWTH factors , *BILIARY tract , *COLLAGEN , *TRETINOIN - Abstract
Abstract: Transforming growth factor-beta1 (TGF-β1) mediates expression of collagen 1A2 (Col 1A2) gene via a synergistic cooperation between Smad2/Smad3 and Sp1, both act on the Col 1A2 gene promoter. In our previous study, we reported that a retinoic acid derivative obtained from Phellinus linteus (designated PL) antagonizes TGF-β-induced liver fibrosis through regulation of ROS and calcium influx. In this continuing study we seek further the effect of PL on the Smad signaling pathway. We used a Col 1A2 promoter-luciferase construct to study the action of PL on Smad through TGF-β. We found that PL decreases the promoter activity of Col 1A2, hinders the translocalization of phosphorylated Smad2/3–Smad 4 complex from cytosol into nucleus and inhibits Sp1 binding activity. These results suggest that PL inhibits TGF-β1-induced Col 1A2 promoter activity through blocking ROS and calcium influx as well as impeding Sp1 binding and translocalization of pSmad 2/3–Smad4 complex into nucleus. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF