Journal of the Formosan Medical Association (Feb 2017)

Epigallocatechin-3-gallate inhibits transforming-growth-factor-β1-induced collagen synthesis by suppressing early growth response-1 in human buccal mucosal fibroblasts

  • Yu-Ping Hsieh,
  • Hsin-Ming Chen,
  • Hung-Ying Lin,
  • Hsiang Yang,
  • Jenny Zwei-Chieng Chang

DOI
https://doi.org/10.1016/j.jfma.2016.01.014
Journal volume & issue
Vol. 116, no. 2
pp. 107 – 113

Abstract

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Transforming growth factor (TGF)-β is a key regulator in the pathogenesis of oral submucous fibrosis (OSF). Early growth response (Egr)-1 is essential for fibrotic responses to TGF-β. Because TGF-β signaling is cell-type- and context-dependent, we investigated the signaling involved in TGF-β-induced Egr-1 in primary human buccal mucosal fibroblasts (BMFs). Methods: TGF-β-induced Egr-1 and its signaling were assessed by western blotting in BMFs. Egr-1 small interfering RNA was used to define the role of Egr-1 on TGF-β-induced mRNAs of the α1- and α2-chains of type I collagen (COL1A1 and COL1A2) and acid-soluble collagen production (via Sircol collagen assay). The effects of epigallocatechin-3-gallate (EGCG) on TGF-β-induced Egr-1 protein and acid-soluble collagen were also evaluated. Results: TGF-β1 stimulated Egr-1 production in BMFs. Pretreatment with PD98059, SP600125, SB431542, and SIS3, but not SB203580, significantly reduced TGF-β1-induced Egr-1 protein expression. Genetic targeting of Egr-1 completely inhibited TGF-β1-induced type I collagen mRNAs and collagen protein expression. EGCG fully inhibited TGF-β1-induced Egr-1 and TGF-β1-stimulated production of acid-soluble collagens. Conclusion: We conclude that activin receptor-like kinase (ALK)5, Smad3, extracellular signal-regulated kinase, and c-Jun N-terminal kinase are involved in the TGF-β1-induced Egr-1 protein production in BMFs. Egr-1 mediates TGF-β1-induced COL1A1 and COL1A2 mRNA expression and acid-soluble collagen production in BMFs. EGCG can block TGF-β1-induced collagen production by attenuating Egr-1 expression in BMFs. Egr-1 is a key mediator in TGF-β1-induced pathogenesis of OSF. EGCG may be useful in the prevention or treatment of OSF.

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