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

doi:10.1016/j.bbrc.2008.05.192

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

Department of Emergency Medicine

Research output: Contribution to journal › Article › peer-review

22 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 language	English
Pages (from-to)	219-223
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	373
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2008.05.192
Publication status	Published - 2008 Aug 22

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.05.192

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@article{64f79d6e90aa45f9b98c4463f3005739,

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

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.",

author = "Yang, {Kun Lin} and Chang, {Wen Teng} and Hung, {Kuo Chen} and Li, {Eric I.C.} and Chuang, {Chia Chang}",

note = "Funding Information: We are greatly indebted to Professor Maria Trojanowska, Medical University of South Carolina, for providing Col 1A2 promoter-luciferase construct, and Professor Paturu Kondaiah, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, India, for pPk9a. We also gratefully acknowledge the kind provision of HSC-T6 cells by Dr. Scott L. Friedman, Division of Liver Diseases, the Mount Sinai School of Medicine, New York, USA. This work was partially supported by a grant from the National Science Council, Taiwan (NSC 93-2622-B- 006-002-CC3). We also thank the Geneferm Biotech Co. Ltd., Taiwan for providing retinoic acid derivative.",

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doi = "10.1016/j.bbrc.2008.05.192",

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T1 - Inhibition of transforming growth factor-β-induced liver fibrosis by a retinoic acid derivative via the suppression of Col 1A2 promoter activity

AU - Yang, Kun Lin

AU - Chang, Wen Teng

AU - Hung, Kuo Chen

AU - Li, Eric I.C.

AU - Chuang, Chia Chang

N1 - Funding Information: We are greatly indebted to Professor Maria Trojanowska, Medical University of South Carolina, for providing Col 1A2 promoter-luciferase construct, and Professor Paturu Kondaiah, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, India, for pPk9a. We also gratefully acknowledge the kind provision of HSC-T6 cells by Dr. Scott L. Friedman, Division of Liver Diseases, the Mount Sinai School of Medicine, New York, USA. This work was partially supported by a grant from the National Science Council, Taiwan (NSC 93-2622-B- 006-002-CC3). We also thank the Geneferm Biotech Co. Ltd., Taiwan for providing retinoic acid derivative.

PY - 2008/8/22

Y1 - 2008/8/22

N2 - 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.

AB - 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.

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

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