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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

RETRACTION: Indole-3-Carbinol Enhances the Resolution of Rat Liver Fibrosis and Stimulates Hepatic Stellate Cell Apoptosis by Blocking the Inhibitor of κB Kinase α/Inhibitor of κB-α/Nuclear Factor-κB Pathway

Jie Ping, Ai-mei Gao, Hai-quan Qin, Xiao-ning Wei, Jing Bai, Lian Liu, Xiao-hai Li, Rui-wen Li, Ying Ao and Hui Wang
Journal of Pharmacology and Experimental Therapeutics November 2011, 339 (2) 694-703; DOI: https://doi.org/10.1124/jpet.111.179820
Jie Ping
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Ai-mei Gao
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Hai-quan Qin
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Xiao-ning Wei
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Jing Bai
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Lian Liu
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Xiao-hai Li
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Rui-wen Li
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Ying Ao
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Hui Wang
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This article has been retracted. Please see:

  • Notice of Retraction - July 01, 2012

Abstract

Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the clearance of activated HSC by apoptosis is associated with the resolution of liver fibrosis. The development of strategies that promote this process in a selective way is therefore important. We evaluated the effects of indole-3-carbinol (I3C), a nutritional component derived from vegetables from the Brassica family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of I3C were monitored in three rat models of liver fibrosis induced by porcine serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line. The results showed that I3C treatment significantly reduced the number of activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C reduced hepatocyte degeneration and necrosis, accelerated collagen degradation, and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the expression ratio of Bax to Bcl-2. High-throughput protein array analysis indicated that the tumor necrosis factor-α/nuclear factor-κB (NF-κB) signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and electrophoretic mobility-shift assay confirmed that I3C inhibited the phosphorylation of inhibitor of κB kinase α and inhibitor of κB-α and NF-κB DNA binding activity. In conclusion, I3C could promote the reverse process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro, which indicates the use of I3C as a potential therapeutic agent in liver fibrosis treatment.

Footnotes

  • This work was supported by the National Nature Science Foundation of China [Grants 30800931, 30371666] and the Natural Science Foundation of Hubei Province, China [Grant 2008CDB117].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.179820.

  • ABBREVIATIONS:

    ECM
    extracellular matrix
    HSC
    hepatic stellate cells
    α-SMA
    α-smooth muscle actin
    I3C
    indole-3-carbinol
    IKKα
    inhibitor of κB kinase α
    p-IKKα
    phospho-IKKα
    IκB-α
    inhibitor of κB-α
    p-IκB-α
    phospho-IκB-α
    NF-κB
    nuclear factor-κB
    DMSO
    dimethyl sulfoxide
    DMEM
    Dulbecco's modified Eagle's medium
    FBS
    fetal bovine serum
    TNFα
    tumor necrosis factor-α
    PS
    porcine serum
    BDL
    bile duct ligation
    MHT
    multiple hepatotoxic
    PBS
    phosphate-buffered saline
    HE
    hematoxylin and eosin
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    EMSA
    electrophoretic mobility-shift assay
    FITC
    fluorescein isothiocyanate
    DIM
    3,3′-diindolylmethane
    PCR
    polymerase chain reaction.

  • Received January 24, 2011.
  • Accepted August 19, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 339 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 339, Issue 2
1 Nov 2011
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Indole-3-Carbinol Enhances Resolution of Liver Fibrosis

Jie Ping, Ai-mei Gao, Hai-quan Qin, Xiao-ning Wei, Jing Bai, Lian Liu, Xiao-hai Li, Rui-wen Li, Ying Ao and Hui Wang
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 694-703; DOI: https://doi.org/10.1124/jpet.111.179820

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Indole-3-Carbinol Enhances Resolution of Liver Fibrosis

Jie Ping, Ai-mei Gao, Hai-quan Qin, Xiao-ning Wei, Jing Bai, Lian Liu, Xiao-hai Li, Rui-wen Li, Ying Ao and Hui Wang
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 694-703; DOI: https://doi.org/10.1124/jpet.111.179820
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