Role of TGF-β and BMP7 in the Pathogenesis of Oral Submucous Fibrosis

Growth Factors. 2011 Aug;29(4):119-27. doi: 10.3109/08977194.2011.582839. Epub 2011 May 19.

Abstract

To understand the molecular pathogenesis of oral submucous fibrosis (OSF), which is a chronic inflammatory disease, gene expression profiling was performed in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results revealed differential expression of 5,288 genes (P ≤ 0.05 and fold change ≥ 1.5). Among these, 2,884 are upregulated and 2,404 are downregulated. Validation employing quantitative real-time PCR and immunohistochemistry confirmed upregulation of transforming growth factor-β1 (TGF-β1), TGFBIp, THBS1, SPP1, and TIG1 and downregulation of bone morphogenic protein 7 (BMP7) in OSF tissues. Furthermore, activation of TGF-β pathway was evident in OSF as demonstrated by pSMAD2 strong immunoreactivity. Treatment of keratinocytes and oral fibroblasts by TGF-β confirmed the regulation of few genes identified in microarray including upregulation of connective tissue growth factor, TGM2, THBS1, and downregulation of BMP7, which is a known negative modulator of fibrosis. Taken together, these data suggest activation of TGF-β signaling and suppression of BMP7 expression in the manifestation of OSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 7 / biosynthesis
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism*
  • Cell Line
  • Fibroblasts / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Inflammation
  • Keratinocytes / drug effects
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / pathology
  • Oligonucleotide Array Sequence Analysis
  • Oral Submucous Fibrosis / genetics*
  • Oral Submucous Fibrosis / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta