|Title:||Activation of transforming growth factor-β1 by thrombin via integrins αvβ1, αvβ3, and αvβ5 in buccal fibroblasts: Suppression by epigallocatechin-3-gallate||Authors:||JENNY ZWEI-CHIENG CHANG
|Issue Date:||2017||Publisher:||John Wiley and Sons Inc.||Journal Volume:||39||Journal Issue:||7||Start page/Pages:||1436-1445||Source:||Head and Neck||Abstract:||
Background: Transforming growth factor-beta (TGF-β) plays a central role in the pathogenesis of oral submucous fibrosis (OSF). Thrombin is a key player in tissue repair, inflammation, and fibrosis after injury. Methods: Effects of thrombin on activated-TGF-β1 levels, Smad3 phosphorylation, and connective tissue growth factor (CTGF/CCN2) synthesis in primary human buccal mucosal fibroblasts (BMFs) were assessed by enzyme-linked immunosorbent assay or Western blot analysis. Results: Thrombin and protease-activated receptor-1 (PAR-1) agonist induced TGF-β1 activation and Smad3 phosphorylation. Pretreatment with TGF-β-neutralizing antibody completely inhibited thrombin-induced CCN2 synthesis. Neutralizing antibodies to integrin αv, β1, αvβ3, αvβ5, and Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor Y27632 completely blocked thrombin-induced TGF-β1 activation, Smad3 phosphorylation, and CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited thrombin-induced TGF-β1 activation. Conclusion: Thrombin induces αvβ1, αvβ3, and αvβ5 integrins-mediated TGF-β1 activations via ROCK signaling. EGCG inhibits thrombin-induced CCN2 synthesis in BMFs by suppressing latent TGF-β1 activation. ? 2017 Wiley Periodicals, Inc.
|ISSN:||1043-3074||DOI:||10.1002/hed.24791||SDG/Keyword:||4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide; alphaVbeta1 integrin; alphaVbeta5 integrin; connective tissue growth factor; epigallocatechin gallate; integrin; neutralizing antibody; Smad3 protein; thrombin; transforming growth factor beta1; unclassified drug; vitronectin receptor; alphaVbeta5 integrin; catechin; epigallocatechin gallate; integrin alphavbeta1; thrombin; transforming growth factor beta1; vitronectin receptor; Article; cheek cell; controlled study; enzyme linked immunosorbent assay; fibroblast; human; human cell; priority journal; protein phosphorylation; protein synthesis; Western blotting; analogs and derivatives; cell culture; drug effects; fibroblast; metabolism; mouth disease; mouth mucosa; pathology; procedures; sensitivity and specificity; Blotting, Western; Catechin; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Humans; Integrin alphaVbeta3; Mouth Mucosa; Oral Submucous Fibrosis; Receptors, Vitronectin; Sensitivity and Specificity; Thrombin; Transforming Growth Factor beta1
|Appears in Collections:||牙醫學系|
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