Experimental study on TGF-β1-mediated CD147 expression in oral submucous fibrosis

Oral Dis. 2018 Sep;24(6):993-1000. doi: 10.1111/odi.12845. Epub 2018 Jun 7.

Abstract

Objective: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown.

Methods: In this study, we investigated the expression of CD147 and transforming growth factor β1 (TGF-β1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-β1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-β1 or LY2157299, an inhibitor of TGF-β1 receptor and arecoline stimulation.

Results: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-β1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-β1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-β1 down-regulated CD147 expression.

Conclusion: Our findings suggest arecoline promotes CD147 expression via the TGF-β1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

Keywords: CD147; arecoline; oral submucous fibrosis; transforming growth factor 1.

MeSH terms

  • Arecoline / pharmacology
  • Basigin / metabolism*
  • Cells, Cultured
  • Cholinergic Agonists / pharmacology
  • Humans
  • Keratinocytes / metabolism*
  • Mouth Mucosa / metabolism*
  • Oral Submucous Fibrosis / metabolism*
  • Pyrazoles / pharmacology
  • Quinolines / pharmacology
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Up-Regulation / drug effects

Substances

  • BSG protein, human
  • Cholinergic Agonists
  • Pyrazoles
  • Quinolines
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Basigin
  • Arecoline
  • LY-2157299