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Clinical Oral Investigations

Published in:

01-03-2013 | Original Article

EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts

Authors: Jenny Zwei-Chieng Chang, Wan-Hsien Yang, Yi-Ting Deng, Hsin-Ming Chen, Mark Yen-Ping Kuo

Published in: Clinical Oral Investigations | Issue 2/2013

Abstract

Objectives

Transforming growth factor β (TGFβ) has been suggested as the main trigger for the increased collagen production and decreased matrix degradation pathways in oral submucous fibrosis (OSF). Connective tissue growth factor (CTGF/CCN2) and cyclooxygenase-2 (COX-2) were found to overexpress in OSF. The aim of this study was to investigate the molecular mechanism underlying the TGFβ-induced CCN2 expressions in human buccal mucosal fibroblasts (BMFs) to identify the potential targets for drug intervention or chemoprevention of OSF.

Materials and methods

TGFβ-induced CCN2 expression and its signaling pathways were assessed by Western blot analyses in BMFs.

Results

TGFβ1 stimulated CCN2 synthesis in BMFs. Pretreatment with c-Jun NH₂-terminal kinase (JNK) inhibitor SP600125, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and activin receptor-like kinase 5 (ALK5) inhibitor SB431542 significantly reduced TGFβ1-induced CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) completely blocked TGFβ1-induced CCN2 synthesis by inhibiting the phosphorylation of JNK and p38 MAPK. Prostaglandin E₂ (PGE₂) inhibited the TGFβ1-induced CCN2 synthesis in human fetal lung fibroblasts IMR90 but not in BMFs.

Conclusions

The TGFβ1-induced CCN2 synthesis in BMFs could be mediated by the ALK5, JNK, and p38 MAPK pathways. EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in BMFs.

Clinical relevance

The exceptional signal transduction pathways of TGFβ1-induced CCN2 production in BMFs contribute to the resistance of PGE₂ downregulation of CCN2 expression; therefore, the CTGF/CCN2 levels are maintained in the OSF tissues in the presence of COX-2. EGCG may serve as a useful agent in controlling OSF.

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Title: EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts
Authors: Jenny Zwei-Chieng Chang
Wan-Hsien Yang
Yi-Ting Deng
Hsin-Ming Chen
Mark Yen-Ping Kuo
Publication date: 01-03-2013
Publisher: Springer-Verlag
Published in: Clinical Oral Investigations / Issue 2/2013
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-012-0713-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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