Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis-a precancer condition

被引:49
作者
Chang, Mei-Chi [1 ]
Lin, Li-Deh [2 ,3 ,4 ]
Wu, Hui-Lin [5 ]
Ho, Yuan-Soon [6 ]
Hsien, Hsiang-Chi [7 ]
Wang, Tong-Mei [2 ,3 ,4 ]
Jeng, Po-Yuan [2 ,3 ,4 ]
Cheng, Ru-Hsiu [2 ,3 ,4 ]
Hahn, Liang-Jiunn [2 ,3 ,4 ]
Jeng, Jiiang-Huei [2 ,3 ,4 ]
机构
[1] Chang Gung Univ Sci & Technol, Biomed Sci Team, Tao Yuan, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Dent, Lab Pharmacol Toxicol Carcinogenesis, Taipei, Taiwan
[3] Natl Taiwan Univ Hosp, Sch Dent, Taipei, Taiwan
[4] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan
[5] Natl Taiwan Univ Hosp, Hepatitis Res Ctr, Taipei, Taiwan
[6] Taipei Med Univ, Dept Biotechnol, Taipei, Taiwan
[7] Chang Gung Mem Hosp, Dept Dent, Lin Kou Branch, Tao Yuan, Taiwan
关键词
COLLAGEN LATTICE CONTRACTION; LIGHT-CHAIN KINASE; CELL-CYCLE ARREST; RHO-KINASE; IN-VITRO; GINGIVAL FIBROBLASTS; MATRIX CONTRACTION; PROSTAGLANDIN E-2; EPITHELIAL-CELLS; MESSENGER-RNA;
D O I
10.1093/carcin/bgt012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Betel quid (BQ) chewing is an oral habit that increases the risk of oral cancer and oral submucous fibrosis (OSF), a precancerous condition showing epithelial atrophy and tissue fibrosis. Persistent fibroblast contraction may induce the fibrotic contracture of tissue. In this study, we found that areca nut extract (ANE) (2001200 g/ml) stimulated buccal mucosa fibroblast (OMF)-populated collagen gel contraction. Arecoline but not arecaidineutwo areca alkaloids, slightly induced the OMF contraction. Exogenous addition of carboxylesterase (2U/ml) prevented the arecoline- but not ANE-induced OMF contraction. OMF expressed inositol triphosphate (IP3) receptors. ANE-induced OMF (800 g/ml) contraction was inhibited by U73122 [phospholipase C (PLC) inhibitor] and 2-aminoethoxydiphenyl borate (IP3 receptor antagonist), respectively. Ethylene glycol tetraacetic acid and verapamil, two calcium mobilization modulators, also suppressed the ANE-induced OMF contraction. ANE induced calcium/calmodulin kinase II and myosin light chain (MLC) phosphorylation in OMF. Moreover, W7 (a Ca-2/calmodulin inhibitor), HA1077 (Rho kinase inhibitor), ML-7 (MLC kinase inhibitor) and cytochalasin B (actin filament polymerization inhibitor) inhibited the ANE-induced OMF contraction. Although ANE elevated reactive oxygen species (ROS) level in OMF, catalase, superoxide dismutase and N-acetyl-l-cysteine showed no obvious effect on ANE-elicited OMF contraction. These results indicate that BQ chewing may affect the wound healing and fibrotic processes in OSF via inducing OMF contraction by ANE and areca alkaloids. AN components-induced OMF contraction was related to PLC/IP3/Ca-2/calmodulin and Rho signaling pathway as well as actin filament polymerization, but not solely due to ROS production.
引用
收藏
页码:1096 / 1104
页数:9
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