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

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.

• Authors: Jenny Zwei-Chieng Chang, Wan-Hsien Yang, Yi-Ting Deng, Hsin-Ming Chen, Mark Yen-Ping Kuo
• Journal: Head & neck (Head Neck) Vol. 34 Issue 8 Pg. 1089-94 (Aug 2012) ISSN: 1097-0347 [Electronic] United States
• PMID: 21953860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Amino Acid Chloromethyl Ketones
• Anticarcinogenic Agents
• CCN2 protein, human
• Hemostatics
• Reactive Oxygen Species
• Receptor, PAR-1
• Serine Proteinase Inhibitors
• Connective Tissue Growth Factor
• Catechin
• epigallocatechin gallate
• JNK Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 5
• Thrombin
• phenylalanyl-prolyl-arginine-chloromethyl ketone

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Anticarcinogenic Agents (pharmacology)
• Areca
• Blotting, Western
• Catechin (analogs & derivatives, pharmacology)
• Cells, Cultured
• Connective Tissue Growth Factor (metabolism)
• Fibroblasts (metabolism)
• Hemostatics (pharmacology)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Kinase Kinase 5 (metabolism)
• Mastication
• Mouth Mucosa (cytology)
• Oral Submucous Fibrosis (metabolism)
• Reactive Oxygen Species (metabolism)
• Receptor, PAR-1 (metabolism)
• Serine Proteinase Inhibitors (pharmacology)
• Thrombin (pharmacology)
• Up-Regulation