Khan Imran, Agarwal Prasoon, Thangjam Gagan Singh, Radhesh Rekha, Rao S Girish, Kondaiah Paturu
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, 560012, Bangalore, India.
Growth Factors. 2011 Aug;29(4):119-27. doi: 10.3109/08977194.2011.582839. Epub 2011 May 19.
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.
为了解作为一种慢性炎症性疾病的口腔黏膜下纤维化（OSF）的分子发病机制，利用寡核苷酸芯片对10例OSF组织和8份正常组织混合样本进行了基因表达谱分析。微阵列结果显示5288个基因存在差异表达（P≤0.05且倍数变化≥1.5）。其中，2884个基因上调，2404个基因下调。采用定量实时PCR和免疫组织化学进行验证，证实OSF组织中转化生长因子-β1（TGF-β1）、TGFBIp、THBS1、SPP1和TIG1上调，骨形态发生蛋白7（BMP7）下调。此外，pSMAD2强免疫反应性表明OSF中TGF-β信号通路被激活。用TGF-β处理角质形成细胞和口腔成纤维细胞，证实了微阵列中鉴定出的少数基因的调控情况，包括结缔组织生长因子、TGM2、THBS1上调，以及BMP7下调，BMP7是一种已知的纤维化负调节因子。综上所述，这些数据表明在OSF的发生过程中TGF-β信号通路被激活，BMP7表达受到抑制。
