Thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production in human buccal mucosal fibroblasts: Inhibition by epigallocatechin-3-gallate
Journal
Head and Neck
Journal Volume
34
Journal Issue
8
Pages
1089-1094
Date Issued
2012
Author(s)
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 NH 2-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 NH 2-terminal kinase pathways and prevented by epigallocatechin-3-gallate. ? 2011 Wiley Periodicals, Inc. Head Neck, 2012 Copyright ? 2011 Wiley Periodicals, Inc.
SDGs
Other Subjects
acetylcysteine; anthra[1,9 cd]pyrazol 6(2h) one; antioxidant; apoptosis signal regulating kinase 1; connective tissue growth factor; enzyme inhibitor; epigallocatechin gallate; proteinase activated receptor 1; reactive oxygen metabolite; stress activated protein kinase inhibitor; thioredoxin; thrombin; apoptosis; article; buccal mucosal fibroblast; fibroblast; human; human cell; injury; mouth disease; priority journal; protein expression; protein synthesis; signal transduction; Western blotting; Amino Acid Chloromethyl Ketones; Anticarcinogenic Agents; Areca; Blotting, Western; Catechin; Cells, Cultured; Connective Tissue Growth Factor; Fibroblasts; Hemostatics; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinase 5; Mastication; Mouth Mucosa; Oral Submucous Fibrosis; Reactive Oxygen Species; Receptor, PAR-1; Serine Proteinase Inhibitors; Thrombin; Up-Regulation
Type
journal article