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

Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis.

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1
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, 560012, Bangalore, India.

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.

PMID:
21591998
DOI:
10.3109/08977194.2011.582839
[Indexed for MEDLINE]

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