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Clinical Oral Investigations
Erschienen in: Clinical Oral Investigations 2/2013

01.03.2013 | Original Article

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

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

Erschienen in: Clinical Oral Investigations | Ausgabe 2/2013

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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.
Literatur
1.
Rajalalitha P, Vali S (2005) Molecular pathogenesis of oral submucous fibrosis—a collagen metabolic disorder. J Oral Pathol Med 34:321–328PubMedCrossRef
2.
Angadi PV, Rao SS (2011) Areca nut in pathogenesis of oral submucous fibrosis: revisited. Oral Maxillofac Surg 15:1–9PubMedCrossRef
3.
Moutasim KA, Jenei V, Sapienza K, Marsh D, Weinreb PH, Violette SM et al (2011) Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis. J Pathol 223:366–377PubMedCrossRef
4.
Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S (2006) Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 42:561–568PubMedCrossRef
5.
Huang CH, Shieh TY (1999) Immunohistochemical expression of transforming growth factor beta in oral submucous fibrosis. J Acad Formos Stomatol 15:227–239
6.
Tian M, Neil JR, Schiemann WP (2011) Transforming growth factor-beta and the hallmarks of cancer. Cell Signal 23:951–962PubMedCrossRef
7.
Wrzesinski SH, Wan YY, Flavell RA (2007) Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res 13:5262–5270PubMedCrossRef
8.
Lau LF, Lam SC (1999) The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res 248:44–57PubMedCrossRef
9.
Leask A, Abraham DJ (2004) TGF-beta signaling and the fibrotic response. FASEB J 18:816–827PubMedCrossRef
10.
Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A (2001) CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem 276:10594–10601PubMedCrossRef
11.
Leask A, Sa S, Holmes A, Shiwen X, Black CM, Abraham DJ (2001) The control of ccn2 (ctgf) gene expression in normal and scleroderma fibroblasts. Mol Pathol 54:180–183PubMedCrossRef
12.
Haydont V, Riser BL, Aigueperse J, Vozenin-Brotons MC (2008) Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-beta1. Am J Physiol Cell Physiol 294:C1332–C1341PubMedCrossRef
13.
Deng YT, Chen HM, Cheng SJ, Chiang CP, Kuo MY (2009) Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: modulation by curcumin. Oral Oncol 45:e99–e105PubMedCrossRef
14.
Black SA Jr, Palamakumbura AH, Stan M, Trackman PC (2007) Tissue-specific mechanisms for CCN2/CTGF persistence in fibrotic gingiva: interactions between cAMP and MAPK signaling pathways, and prostaglandin E2-EP3 receptor mediated activation of the c-JUN N-terminal kinase. J Biol Chem 282:15416–15429PubMedCrossRef
15.
Stratton R, Rajkumar V, Ponticos M, Nichols B, Shiwen X, Black CM et al (2002) Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathway. FASEB J 16:1949–1951PubMed
16.
Duncan MR, Frazier KS, Abramson S, Williams S, Klapper H, Huang X et al (1999) Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis: down-regulation by cAMP. FASEB J 13:1774–1786PubMed
17.
Chang JZ, Yang W, Deng Y, Chen H, Kuo MY (2011) Thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production in human buccal mucosal fibroblasts: inhibition by epigallocatechin-3-gallate. Head Neck. doi:10.​1002/​hed.​21863
18.
Tsai CH, Chou MY, Chang YC (2003) The up-regulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med 32:146–153PubMedCrossRef
19.
Prime SS, Pring M, Davies M, Paterson IC (2004) TGF-beta signal transduction in oro-facial health and non-malignant disease (part I). Crit Rev Oral Biol Med 15:324–336PubMedCrossRef
20.
21.
Shi-wen X, Stanton LA, Kennedy L, Pala D, Chen Y, Howat SL et al (2006) CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts. J Biol Chem 281:10715–10726PubMedCrossRef
22.
Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM et al (2007) Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 56:323–333PubMedCrossRef
23.
Kang JS, Liu C, Derynck R (2009) New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol 19:385–394PubMedCrossRef
24.
25.
Thompson K, Hamilton DW, Leask A (2010) ALK5 inhibition blocks TGF-beta-induced CCN2 expression in gingival fibroblasts. J Dent Res 89:1450–1454PubMedCrossRef
26.
Cicha I, Goppelt-Struebe M (2009) Connective tissue growth factor: context-dependent functions and mechanisms of regulation. Biofactors 35:200–208PubMedCrossRef
27.
Sriram N, Kalayarasan S, Sudhandiran G (2009) Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis. Chem Biol Interact 180:271–280PubMedCrossRef
28.
Tipoe GL, Leung TM, Liong EC, Lau TY, Fung ML, Nanji AA (2010) Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced liver injury in mice. Toxicology 273:45–52PubMedCrossRef
29.
Hao J, Kim CH, Ha TS, Ahn HY (2007) Epigallocatechin-3 gallate prevents cardiac hypertrophy induced by pressure overload in rats. J Vet Sci 8:121–129PubMedCrossRef
30.
Dooley A, Shi-Wen X, Aden N, Tranah T, Desai N, Denton CP et al (2010) Modulation of collagen type I, fibronectin and dermal fibroblast function and activity, in systemic sclerosis by the antioxidant epigallocatechin-3-gallate. Rheumatology (Oxford) 49:2024–2036CrossRef
Metadaten
Titel
EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts
verfasst von
Jenny Zwei-Chieng Chang
Wan-Hsien Yang
Yi-Ting Deng
Hsin-Ming Chen
Mark Yen-Ping Kuo
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Clinical Oral Investigations / Ausgabe 2/2013
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-012-0713-5

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