EGCG blocks TGFß1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts.
Clin Oral Investig
; 17(2): 455-61, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-22415218
ABSTRACT
OBJECTIVES:
Transforming growth factor ß (TGFß) 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 TGFß-induced CCN2 expressions in human buccal mucosal fibroblasts (BMFs) to identify the potential targets for drug intervention or chemoprevention of OSF. MATERIALS ANDMETHODS:
TGFß-induced CCN2 expression and its signaling pathways were assessed by Western blot analyses in BMFs.RESULTS:
TGFß1 stimulated CCN2 synthesis in BMFs. Pretreatment with c-Jun NH(2)-terminal kinase (JNK) inhibitor SP600125, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and activin receptor-like kinase 5 (ALK5) inhibitor SB431542 significantly reduced TGFß1-induced CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) completely blocked TGFß1-induced CCN2 synthesis by inhibiting the phosphorylation of JNK and p38 MAPK. Prostaglandin E(2) (PGE(2)) inhibited the TGFß1-induced CCN2 synthesis in human fetal lung fibroblasts IMR90 but not in BMFs.CONCLUSIONS:
The TGFß1-induced CCN2 synthesis in BMFs could be mediated by the ALK5, JNK, and p38 MAPK pathways. EGCG blocks TGFß1-induced CCN2 by suppressing JNK and p38 in BMFs. CLINICAL RELEVANCE The exceptional signal transduction pathways of TGFß1-induced CCN2 production in BMFs contribute to the resistance of PGE(2) 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
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Catequina
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MAP Quinase Quinase 4
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Proteínas Quinases p38 Ativadas por Mitógeno
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Fator de Crescimento Transformador beta1
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Fator de Crescimento do Tecido Conjuntivo
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Fibroblastos
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Mucosa Bucal
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article