Activation of transforming growth factor-1 by thrombin via integrins v1, v3, and v5 in buccal fibroblasts: Suppression by epigallocatechin-3-gallate

被引：23

作者：

Chang, Jenny Zwei-Chieng ^{[1
,2
]}

Hsieh, Yu-Ping ^{[1
]}

Lin, Wen-Hsin ^{[1
]}

Chen, Hsin-Ming ^{[1
,2
]}

Kuo, Mark Yen-Ping ^{[1
,2
]}

机构：

[1] Natl Taiwan Univ, Sch Dent, Coll Med, 1 Chang De St, Taipei 100, Taiwan

[2] Natl Taiwan Univ Hosp, Dept Dent, Taipei, Taiwan

来源：

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK | 2017年 / 39卷 / 07期

关键词：

epigallocatechin-3-gallate (EGCG); fibroblast; oral submucous fibrosis; thrombin; transforming growth factor-beta (TGF-); ORAL SUBMUCOUS FIBROSIS; TGF-BETA ACTIVATION; GINGIVAL FIBROBLASTS; MEDIATED ACTIVATION; SIGNALING PATHWAYS; GREEN TEA; RECEPTOR-1; EXPRESSION; PATHOGENESIS; TRANSFORMING-GROWTH-FACTOR-BETA-1;

D O I：

10.1002/hed.24791

中图分类号：

R76 [耳鼻咽喉科学];

学科分类号：

100213 ;

摘要：

BackgroundTransforming growth factor-beta (TGF-) plays a central role in the pathogenesis of oral submucous fibrosis (OSF). Thrombin is a key player in tissue repair, inflammation, and fibrosis after injury. MethodsEffects of thrombin on activated-TGF-1 levels, Smad3 phosphorylation, and connective tissue growth factor (CTGF/CCN2) synthesis in primary human buccal mucosal fibroblasts (BMFs) were assessed by enzyme-linked immunosorbent assay or Western blot analysis. ResultsThrombin and protease-activated receptor-1 (PAR-1) agonist induced TGF-1 activation and Smad3 phosphorylation. Pretreatment with TGF--neutralizing antibody completely inhibited thrombin-induced CCN2 synthesis. Neutralizing antibodies to integrin v, 1, v3, v5, and Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor Y27632 completely blocked thrombin-induced TGF-1 activation, Smad3 phosphorylation, and CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited thrombin-induced TGF-1 activation. ConclusionThrombin induces v1, v3, and v5 integrins-mediated TGF-1 activations via ROCK signaling. EGCG inhibits thrombin-induced CCN2 synthesis in BMFs by suppressing latent TGF-1 activation.

引用

页码：1436 / 1445

页数：10

共 48 条

[1] Targeting the TGFβ signalling pathway in disease [J].

Akhurst, Rosemary J. ;

Hata, Akiko .

NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (10) :790-811

[2] Areca nut in pathogenesis of oral submucous fibrosis: Revisited [J].

Angadi P.V. ;

Rao S.S. .

Oral and Maxillofacial Surgery, 2011, 15 (1) :1-9

[3] Making sense of latent TGFβ activation [J].

Annes, JP ;

Munger, JS ;

Rifkin, DB .

JOURNAL OF CELL SCIENCE, 2003, 116 (02) :217-224

[4] Increased expression of integrin αvβ3 contributes to the establishment of autocrine TGF-β signaling in scleroderma fibroblasts [J].

Asano, Y ;

Ihn, H ;

Yamane, K ;

Jinnin, M ;

Mimura, Y ;

Tamaki, K .

JOURNAL OF IMMUNOLOGY, 2005, 175 (11) :7708-7718

[5] Involvement of αVβ5 integrin-mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts [J].

Asano, Y ;

Ihn, H ;

Yamane, K ;

Jinnin, M ;

Mimura, Y ;

Tamaki, K .

ARTHRITIS AND RHEUMATISM, 2005, 52 (09) :2897-2905

[6] Coming to America Betel nut and oral submucous fibrosis [J].

Aziz, Shahid R. .

JOURNAL OF THE AMERICAN DENTAL ASSOCIATION, 2010, 141 (04) :423-428

[7] Transforming growth factor-β1 (TGFβ1) stimulates connective tissue growth factor (CCN2/CTGF) expression in human gingival fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent mechanism -: Statins with forskolin block TGFβ1-induced CCN2/CTGF expression [J].

Black, Samuel A., Jr. ;

Trackman, Philip C. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (16) :10835-10847

[8] 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].

Black, Samuel A., Jr. ;

Palamakumbura, Amitha H. ;

Stan, Maria ;

Trackman, Philip C. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (21) :15416-15429

[9] Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals [J].

Brigstock, David R. .

JOURNAL OF CELL COMMUNICATION AND SIGNALING, 2010, 4 (01) :1-4

[10] Coagulation cascade proteases and tissue fibrosis [J].

Chambers, RC ;

Laurent, GJ .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2002, 30 :194-200

← 1 2 3 4 5 →