Epigallocatechin-3-gallate inhibits transforming-growth-factor-β1-induced collagen synthesis by suppressing early growth response-1 in human buccal mucosal fibroblasts
Autor: | Jenny Zwei-Chieng Chang, Yu-Ping Hsieh, Hsiang Yang, Hung-Ying Lin, Hsin-Ming Chen |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Small interfering RNA Dioxoles Biology Catechin Collagen Type I fibroblast early growth response-1 Transforming Growth Factor beta1 03 medical and health sciences Extracellular Protein biosynthesis medicine Humans Fibroblast Extracellular Signal-Regulated MAP Kinases transforming growth factor β Cells Cultured oral submucous fibrosis Early Growth Response Protein 1 Medicine(all) Anthracenes Flavonoids lcsh:R5-920 Kinase Mouth Mucosa General Medicine Fibroblasts Molecular biology Cell biology Blot body regions 030104 developmental biology medicine.anatomical_structure Benzamides epigallocatechin-3-gallate lcsh:Medicine (General) Type I collagen hormones hormone substitutes and hormone antagonists Transforming growth factor Signal Transduction |
Zdroj: | Journal of the Formosan Medical Association, Vol 116, Iss 2, Pp 107-113 (2017) |
ISSN: | 0929-6646 |
Popis: | Background/purpose 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. |
Databáze: | OpenAIRE |
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