title: Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis.
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.
authors: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, 560012, Bangalore, India.
authors: Imran
authors: I
authors: Khan
authors: Prasoon
authors: P
authors: Agarwal
authors: Gagan Singh
authors: GS
authors: Thangjam
authors: Rekha
authors: R
authors: Radhesh
authors: S Girish
authors: SG
authors: Rao
authors: Paturu
authors: P
authors: Kondaiah