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Clinical Oral Investigations

Published in:

01-06-2016 | Original Article

Elevated transglutaminase-2 expression mediates fibrosis in areca quid chewing-associated oral submucocal fibrosis via reactive oxygen species generation

Authors: Shiuan-Shinn Lee, Yi-Juai Chen, Chung-Hung Tsai, Fu-Mei Huang, Yu-Chao Chang

Published in: Clinical Oral Investigations | Issue 5/2016

Abstract

Objectives

Transglutaminase-2 (TGM-2) protein is involved in the cross-linking of matrix proteins resulting in several fibrotic disorders and can be induced by reactive oxygen species (ROS). Little is known about its role in the development of oral submucocal fibrosis (OSF). Hence, we hypothesize that TGM-2 may have a role in the pathogenesis of areca quid chewing-associated OSF and arecoline, a major areca nut alkaloid, could regulate TGM-2 via ROS generation.

Materials

Forty OSF specimens from areca quid chewing-associated OSF and ten normal buccal mucosa biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The expression of TGM-2 from fibroblasts cultured from OSF and normal buccal mucosa was evaluated by Western blot. The effect of arecoline on normal buccal mucosa fibroblasts (BMFs) was used to elucidate whether TGM-2 expression could be affected by arecoline by using 2′, 7′-dichlorofluorescein diacetate assay and Western blot. In addition, glutathione precursor N-acetyl-l-cysteine (NAC) and epigallocatechin-3 gallate (EGCG) were added to find the possible regulatory mechanisms.

Results

TGM-2 expression was significantly higher in OSF specimens than normal specimens (p < 0.05). Fibroblasts derived from OSF were found to exhibit higher TGM-2 expression than BMFs in protein levels (p < 0.05). Arecoline significantly upregulated the intracellular ROS generation in a dose-dependent manner (p < 0.05). TGM-2 protein induced by arecoline was found in BMFs in a dose-dependent manner (p < 0.05). Treatment with NAC and EGCG markedly inhibited TGM-2 expression induced by arecoline (p < 0.05).

Conclusions

Our results suggest that TGM-2 expression is significantly upregulated in OSF tissues from areca quid chewers. Arecoline-upregulated TGM-2 expression may be mediated by ROS generation.

Clinical relevance

TGM-2 protein is upregulated in areca quid chewing-associated OSF. Using this in vitro model, antioxidants could inhibit arecoline-upregulated TGM-2 expression. NAC and EGCG may serve as a useful agent in controlling OSF.

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Title: Elevated transglutaminase-2 expression mediates fibrosis in areca quid chewing-associated oral submucocal fibrosis via reactive oxygen species generation
Authors: Shiuan-Shinn Lee
Yi-Juai Chen
Chung-Hung Tsai
Fu-Mei Huang
Yu-Chao Chang
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 5/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-015-1579-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Elevated transglutaminase-2 expression mediates fibrosis in areca quid chewing-associated oral submucocal fibrosis via reactive oxygen species generation

Abstract

Objectives

Materials

Results

Conclusions

Clinical relevance

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Materials

Results

Conclusions

Clinical relevance

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