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

5 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
JournalJournal of Cellular Physiology
DOIs
Publication statusPublished - 2019

Fingerprint

Arecoline
Gastropoda
Mouth Mucosa
Collagen Type I
Myofibroblasts
Oral Submucous Fibrosis
Areca
Fibroblasts
Alkaloids
Chemical activation
Tissue
Down-Regulation
Mucous Membrane
Nuts
Cheek
Carcinogenesis
Fibrosis
Up-Regulation

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa. / Fang, Chih Yuan; Hsia, Shih Min; Hsieh, Pei Ling; Liao, Yi Wen; Peng, Chih Yu; Wu, Ching Zong; Lin, Kuan Chou; Tsai, Lo Lin; Yu, Cheng Chia.

In: Journal of Cellular Physiology, 2019.

Research output: Contribution to journalArticle

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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.",
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AU - Hsia, Shih Min

AU - Hsieh, Pei Ling

AU - Liao, Yi Wen

AU - Peng, Chih Yu

AU - Wu, Ching Zong

AU - Lin, Kuan Chou

AU - Tsai, Lo Lin

AU - Yu, Cheng Chia

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