Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate
Background/Purpose: Oral submucous fibrosis (OSF) is a premalignant condition caused by the chewing of areca nut (AN). Transforming growth factor β (TGFβ) plays a central role in the pathogenesis of OSF. Connective tissue growth factor (CTGF or CCN2) and early growth response-1 (Egr-1) are important...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Journal of the Formosan Medical Association |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664617304849 |
| _version_ | 1818559545184616448 |
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| author | Yu-Ping Hsieh King-Jean Wu Hsin-Ming Chen Yi-Ting Deng |
| author_facet | Yu-Ping Hsieh King-Jean Wu Hsin-Ming Chen Yi-Ting Deng |
| author_sort | Yu-Ping Hsieh |
| collection | DOAJ |
| description | Background/Purpose: Oral submucous fibrosis (OSF) is a premalignant condition caused by the chewing of areca nut (AN). Transforming growth factor β (TGFβ) plays a central role in the pathogenesis of OSF. Connective tissue growth factor (CTGF or CCN2) and early growth response-1 (Egr-1) are important mediators in the fibrotic response to TGFβ in several fibrotic disorders including OSF. Arecoline, a major AN alkaloid, induced the synthesis of CCN2 and Egr-1 in human buccal mucosal fibroblast (BMFs). The aims of this study were to investigate whether arecoline-induced CCN2 and Egr-1 syntheses are mediated through TGFβ1 signaling and to inspect the detailed mechanisms involved. Methods: Western blot and TGFβ1 Emax® ImmunoAssay were used to measure the effect of arecoline on the TGFβ signaling pathways. 2′,7′-dichlorodihydrofluorescein diacetate and MitoSOX™ Red were used to measure the effect of arecoline on the cellular and mitochondrial reactive oxygen species (ROS). Results: Arecoline induced latent TGFβ1 activation, Smad2 phosphorylation, and mitochondrial and total cellular ROS in BMFs. TGFβ-neutralizing antibody completely inhibited the arecoline-induced synthesis of CCN2 and Egr-1. Mito-TEMPO, a mitochondria-targeted antioxidant, completely suppressed arecoline-induced latent TGFβ1 activation and mitochondrial and total cellular ROS. Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited arecoline-induced TGFβ1 activation and mitochondrial ROS in BMFs. Conclusion: Our results indicated that arecoline-induced mitochondrial ROS plays pivotal roles in the activation of latent TGFβ1 leading to the initiation of TGFβ1 signaling and subsequent increase in the synthesis of CCN2 and Egr-1. EGCG can be a useful agent in the chemoprevention and treatment of OSF. Keywords: Areca nut chewing, EGCG, Fibroblast, TGFβ, Oral submucous fibrosis |
| first_indexed | 2024-12-14T00:26:56Z |
| format | Article |
| id | doaj.art-5ee8a7877fa24d3fbdda726a35da8dc7 |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-12-14T00:26:56Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-5ee8a7877fa24d3fbdda726a35da8dc72022-12-21T23:25:00ZengElsevierJournal of the Formosan Medical Association0929-66462018-06-011176527534Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallateYu-Ping Hsieh0King-Jean Wu1Hsin-Ming Chen2Yi-Ting Deng3Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan; Corresponding author. Department of Dentistry, National Taiwan University Hospital Hsin-Chu Branch, 25, Lane 442, Sec. 1, Jingguo Rd., Hsinchu, Taiwan. Fax: +886 23831346.Background/Purpose: Oral submucous fibrosis (OSF) is a premalignant condition caused by the chewing of areca nut (AN). Transforming growth factor β (TGFβ) plays a central role in the pathogenesis of OSF. Connective tissue growth factor (CTGF or CCN2) and early growth response-1 (Egr-1) are important mediators in the fibrotic response to TGFβ in several fibrotic disorders including OSF. Arecoline, a major AN alkaloid, induced the synthesis of CCN2 and Egr-1 in human buccal mucosal fibroblast (BMFs). The aims of this study were to investigate whether arecoline-induced CCN2 and Egr-1 syntheses are mediated through TGFβ1 signaling and to inspect the detailed mechanisms involved. Methods: Western blot and TGFβ1 Emax® ImmunoAssay were used to measure the effect of arecoline on the TGFβ signaling pathways. 2′,7′-dichlorodihydrofluorescein diacetate and MitoSOX™ Red were used to measure the effect of arecoline on the cellular and mitochondrial reactive oxygen species (ROS). Results: Arecoline induced latent TGFβ1 activation, Smad2 phosphorylation, and mitochondrial and total cellular ROS in BMFs. TGFβ-neutralizing antibody completely inhibited the arecoline-induced synthesis of CCN2 and Egr-1. Mito-TEMPO, a mitochondria-targeted antioxidant, completely suppressed arecoline-induced latent TGFβ1 activation and mitochondrial and total cellular ROS. Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited arecoline-induced TGFβ1 activation and mitochondrial ROS in BMFs. Conclusion: Our results indicated that arecoline-induced mitochondrial ROS plays pivotal roles in the activation of latent TGFβ1 leading to the initiation of TGFβ1 signaling and subsequent increase in the synthesis of CCN2 and Egr-1. EGCG can be a useful agent in the chemoprevention and treatment of OSF. Keywords: Areca nut chewing, EGCG, Fibroblast, TGFβ, Oral submucous fibrosishttp://www.sciencedirect.com/science/article/pii/S0929664617304849 |
| spellingShingle | Yu-Ping Hsieh King-Jean Wu Hsin-Ming Chen Yi-Ting Deng Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate Journal of the Formosan Medical Association |
| title | Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate |
| title_full | Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate |
| title_fullStr | Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate |
| title_full_unstemmed | Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate |
| title_short | Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate |
| title_sort | arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts suppression by epigallocatechin 3 gallate |
| url | http://www.sciencedirect.com/science/article/pii/S0929664617304849 |
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