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Antagonism of Transforming Growth Factor-Β Signaling Inhibits Fibrosis-Related Genes

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Abstract

In the fibrotic process, the transforming growth factor-β1 (TGF-β1)/Smad3 (Sma- and Mad-related protein␣3) signaling plays a central role. To screen for antagonists of TGF-β1/Smad3 signaling and to investigate their effects on the genes related to fibrosis, we construct a molecular model with a luciferase reporter gene. Results showed that both SB-431542 [4-(5-benzo[1,3]dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)-benzamide] and small interference RNA (siRNA) against Smad3 could dose-dependently suppress the reporter gene. More importantly, they both significantly inhibited the expression of plasminogen activator inhibitor-type 1 (PAI-1) and type I collagenα1 (Col Iα1) genes in rat hepatic stellate cells. Thus, SB-431542 and Smad3/siRNA may be potential therapeutics for fibrosis.

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Authors and Affiliations

  1. Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China

    Xing-Jun Liu & James Q. Yin

  2. School of Pharmacy, Shengyang Pharmaceutical University, 110016, Shengyang, China

    Xing-Jun Liu, Xian-Feng Gong & Min-Wei Wang

  3. Institute of Pharmacology Toxicology, The Academy of Military Medical Sciences, 100850, Beijing, China

    Cheng-Mai Ruan & Xing-Zhou Li

  4. School of Basic Medicine, China Medical University, 110001, Shenyang, China

    Huai-Liang Wang

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  1. Xing-Jun Liu
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  2. Cheng-Mai Ruan
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  3. Xian-Feng Gong
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  4. Xing-Zhou Li
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  5. Huai-Liang Wang
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  6. Min-Wei Wang
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  7. James Q. Yin
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Correspondence to James Q. Yin.

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Liu, XJ., Ruan, CM., Gong, XF. et al. Antagonism of Transforming Growth Factor-Β Signaling Inhibits Fibrosis-Related Genes. Biotechnol Lett 27, 1609–1615 (2005). https://doi.org/10.1007/s10529-005-2516-0

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  • DOI: https://doi.org/10.1007/s10529-005-2516-0

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