title: Elevation of Twist expression by arecoline contributes to the pathogenesis of oral submucous fibrosis.
abstract: OBJECTIVE
  Oral submucous fibrosis (OSF), a chronic progressive scarring disease, has been considered as a precancerous condition of oral mucosa. In this study, we investigated the functional role of Twist, an epithelial-mesenchymal transition (EMT) transcriptional factor, in myofibroblastic differentiation activity of OSF.
  
  
  METHODS
  Arecoline, a major areca nut alkaloid, was used to explore whether expression of Twist could be changed dose-dependently in human primary buccal mucosal fibroblasts (BMFs). Collagen gel contraction and migration capability in arecoline-stimulated BMFs and primary oral submucous fibrosis-derived fibroblasts (OSFs) with Twist knockdown was presented.
  
  
  RESULTS
  We observed that the treatment of arecoline dose-dependently increased Twist expression transcript and protein levels in BMFs. The myofibroblast activity including collagen gel contraction and migration capability also induced by arecoline, while knockdown of Twist reversed these phenomena. Importantly, inhibition of Twist led to the suppression collagen contraction and wound healing capability of primary cultivated OSFs. Clinically, Twist transcript and protein expression was higher in areca quid chewing-associated OSF tissues than in normal oral mucosa tissues.
  
  
  CONCLUSIONS
  This evidence suggests that upregulation of Twist might be involved in the pathogenesis of areca quid-associated OSF through dysregulation of myofibroblast activity.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Lee
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Li-Chiu
authors.initials: LC
authors.lastname: Yang
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Hu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Peng
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: tao2008@csmu.edu.tw.
authors.forename: Chuan-Hang
authors.initials: CH
authors.lastname: Yu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: ccyu@csmu.edu.tw.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
mesh_terms: D001114:Areca / Q000737:chemistry; D001115:Arecoline / Q000009:adverse effects*; D002478:Cells, Cultured; D006801:Humans; D009061:Mouth Mucosa / Q000473:pathology; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009914:Oral Submucous Fibrosis / Q000235:genetics*; D011230:Precancerous Conditions; D013624:Taiwan; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D001115:Arecoline
keywords: Twist; arecoline; myofibroblasts; oral submucous fibrosis