Vitamin A Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin A, including details on retinol, benefits, dosage, supplements, deficiency, information.

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

Yang KL, Chang WT, Hung KC, Li EI, Chuang CC

Institute of Basic Medical Sciences, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

Transforming growth factor-beta1 (TGF-beta1) 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-beta-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-beta. 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-beta1-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.

Published 7 July 2008 in Biochem Biophys Res Commun, 373(2): 219-23.
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