Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6721-6730
Number of pages10
JournalJournal of Cellular Physiology
Volume234
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • arecoline
  • collagen type I
  • epithelial–mesenchymal transition
  • extracellular matrix
  • myofibroblasts
  • oral submucous fibrosis

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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