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Thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production in human buccal mucosal fibroblasts: Inhibition by epigallocatechin-3-gallate

Authors

  • Jenny Zwei-Chieng Chang DDS, MS*,

    1. School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
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    • *

      The first 2 authors contributed equally to this work.

  • Wan-Hsien Yang MS*,

    1. School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
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    • *

      The first 2 authors contributed equally to this work.

  • Yi-Ting Deng DDS,

    1. School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
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  • Hsin-Ming Chen DDS, PhD,

    1. School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
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  • Mark Yen-Ping Kuo DDS, PhD

    Corresponding author
    1. School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
    • School of Dentistry, College of Medicine and Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
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  • This work was supported by grants from the National Science Council, Taiwan.

Abstract

Background

Connective tissue growth factor (CTGF/CCN2) is associated with many human fibrotic disorders and was found to overexpress in oral submucous fibrosis (OSF). OSF is the result of persistent chemical irritation and microtrauma to oral mucosa from areca nut. Microtrauma could lead to the release of thrombin.

Methods

Thrombin-induced CCN2 expression and its signaling pathways were assessed by Western blot analyses in human buccal mucosal fibroblasts.

Results

Thrombin stimulated CCN2 synthesis in buccal mucosal fibroblasts via activation of protease-activated receptor-1. Pretreatment with antioxidant N-acetyl-L-cysteine, apoptosis signal-regulating kinase 1 inhibitor thioredoxin, and c-Jun NH2-terminal kinase inhibitor SP600125 significantly reduced thrombin-induced CCN2 synthesis. Epigallocatechin-3-gallate completely inhibited thrombin-induced CCN2 synthesis.

Conclusion

Thrombin produced by microtrauma may contribute to the pathogenesis of OSF by up-regulating CCN2 expression. This effect could be mediated by protease-activated receptor-1, reactive oxygen species, apoptosis signal-regulating kinase 1, and c-Jun NH2-terminal kinase pathways and prevented by epigallocatechin-3-gallate. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

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