Inhibition of transforming growth factor-β-induced liver fibrosis by a retinoic acid derivative via the suppression of Col 1A2 promoter activity

Kun Lin Yang, Wen Teng Chang, Kuo Chen Hung, Eric I.C. Li, Chia Chang Chuang

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)219-223
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume373
Issue number2
DOIs
Publication statusPublished - 2008 Aug 22

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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