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Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa |
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| Authors: | Chih-Yuan Fang Shih-Min Hsia Pei-Ling Hsieh Yi-Wen Liao Chih-Yu Peng Ching-Zong Wu Kuan-Chou Lin Lo-Lin Tsai Cheng-Chia Yu |
| Institution: | 1. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Chih-Yuan Fang and Shih-Min Hsia 2. have contributed equally to this work.;3. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan Chih-Yuan Fang and Shih-Min Hsia 4. Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan;5. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan;6. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan;7. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan Department of Dentistry, Lotung PohAi Hospital, Yilan, Taiwan;8. Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;9. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan |
| Abstract: | Epithelial–mesenchymal transition (EMT) has been implicated in fibrogenesis and carcinogenesis; however, the exact role of EMT-inducer Slug in the progression of precancerous oral submucous fibrosis (OSF) has not been investigated. In the current study, we showed that the expression of Slug was upregulated in OSF tissues and associated with various myofibroblast markers. After silence of Slug in fibrotic buccal mucosal fibroblasts (fBMFs), the elevated myofibroblast activities and fibrosis markers were all downregulated. Our data revealed that arecoline, an areca nut alkaloid, increased the expression of Slug in normal BMFs, and inhibition of Slug successfully prevented the arecoline-induced myofibroblast activation. Additionally, overexpression of Slug in BMFs stimulated the activities of myofibroblasts, indicating that upregulation of Slug by arecoline contributes to the myofibroblast transdifferentiation. Most importantly, Slug was able to bind to the E-box of type I collagen, leading to increased expression of type I collagen. Altogether, this study demonstrated the abnormal elevation of Slug in OSF and its significance in arecoline-induced fibrogenesis. Moreover, downregulation of Slug could be a potential target for OSF remedy via suppression of myofibroblast activities and type I collagen. |
| Keywords: | arecoline collagen type I epithelial–mesenchymal transition extracellular matrix myofibroblasts oral submucous fibrosis |