Arecoline Induces LOXL2 Expression via TGF-β Pathway in Buccal Fibroblasts

• Main Authors: ERH-HSIANG WANG, 王爾祥
• Other Authors: Yen-Ping Kuo
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/a9gqt2

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 106 === Lysyl oxidase like protein 2 (LOXL2) is an extracellular copper-dependent amine oxidase that catalyses the cross-linking of collagens and elastin. It has recently been reported to serve a key role in hepatic, renal, and pulmonary fibrosis. Areca nut (AN) chewing is the most important etiological factor in the pathogenesis of oral submucous fibrosis (OSF). We examined the expression of LOXL2 protein in 7 cases of OSF and found elevated LOXL2 staining in fibroblasts and epithelial cells in 6 cases. Arecoline, a main alkaloid found in the areca nut, stimulated LOXL2 synthesis in human buccal mucosal fibroblasts (BMFs). TGFβ-neutralizing antibody, ALK5 specific inhibitor SB431542, Smad3 specific inhibitor SIS3 completely inhibited the arecoline-induced synthesis of LOXL2. Furthermore, TGF-β1 induced LOXL2 expression in BMF. Therefore, arecoline induced LOXL2 expression through TGF-β signal pathway in BMF. Moreover, Pretreated with Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited arecoline-induced LOXL2 expression. In conclusion, EGCG has extreme potential for the prevention or treatment of OSF.