Arecoline enhances miR-21 to promote buccal mucosal fibroblasts activation

Hui Wen Yang, Cheng Chia Yu, Pei Ling Hsieh, Yi Wen Liao, Pei Ming Chu, Chuan Hang Yu, Chih Yuan Fang

Research output: Contribution to journalArticlepeer-review

Abstract

Background/purpose: Oral submucous fibrosis (OSF) is an irreversible fibrosis disease and a potentially malignant disorder in the oral cavity. Various studies have shown that miR-21 was implicated in the fibrogenesis and carcinogenesis, but its functional role in the development of OSF has not been investigated. Methods: The expression levels of miR-21 in arecoline-stimulated normal buccal mucosal fibroblasts (BMFs) and OSF specimens were determined by qRT-PCR. Exogenous administration of TGF-β and its inhibitor (SB431542) were utilized to examine the involvement of TGF-β signaling in miR-21 alteration. Collagen gel contraction, transwell migration, and invasion assays were used to assess the myofibroblast activities. The relationship between α-SMA and miR-21 was calculated using the Pearson correlation coefficient. Results: MiR-21 expression was induced in BMFs by arecoline treatment in a dose-dependent manner. Our results showed that this upregulation was mediated by TGF-β signaling. Subsequently, we demonstrated that the administration of the miR-21 inhibitor suppressed the arecoline-induced myofibroblast characteristics, including a higher collagen gel contractility and cell motility, in normal BMFs. Furthermore, inhibition of miR-21 was sufficient to attenuate the myofibroblast features in fibrotic BMFs. Besides, we showed that the expression of miR-21 was aberrantly upregulated in the OSF tissues and there was a positive correlation between miR-21 and myofibroblast marker, α-SMA. Conclusion: MiR-21 overexpression in OSF may be due to the stimulation of areca nut, which was mediated by the TGF-β pathway. Our data suggested that the repression of miR-21 was a promising direction to palliate the development and progression of OSF.

Original languageEnglish
JournalJournal of the Formosan Medical Association
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • MicroRNA-21
  • Myofibroblast
  • Oral submucous fibrosis
  • TGF-β pathway

ASJC Scopus subject areas

  • Medicine(all)

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