Tsai Chung-Hung, Yang Shun-Fa, Chen Yi-Juai, Chou Ming-Yung, Chang Yu-Chao
Department of Oral Pathology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Oral Oncol. 2005 Oct;41(9):940-6. doi: 10.1016/j.oraloncology.2005.05.006.
Insulin-like growth factor-1 (IGF-1) is a member of a family of two interacting polypeptide hormone ligands with close homology to proinsulin. IGF-1 can influence mesenchymal cell migration, proliferation, and extracellular matrix deposition, thus implicating it in the progression of fibrotic disorders. Currently, there is limited information about the regulation of IGF-1 expression in areca quid-associated oral submucous fibrosis (OSF). The aim of this study was to compare IGF-1 expression in normal human buccal mucosa and OSF specimens and further explore the potential mechanism that may lead to induce IGF-1 expression. Twenty OSF specimens and 10 normal buccal mucosa were examined by immunohistochemistry. The activity of IGF-1 from cells cultured from OSF and normal buccal mucosa were by using reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Furthermore, the effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanism that may lead to induce IGF-1 expression. IGF-1 expression was significantly higher in OSF specimens (p<0.05) and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. OSF demonstrated significantly higher IGF-1 protein expression than normal buccal mucosa fibroblast (BMF) both in mRNA and protein levels (p<0.05). In addition, arecoline was also found to elevate IGF-1 mRNA and protein expression in a dose-dependent manner (p<0.05). Taken together, the data presented here demonstrated that IGF-1 expression is significantly upregulated in OSF from areca quid chewers and arecoline may be responsible for the enhanced IGF-1 expression in vivo.
胰岛素样生长因子-1(IGF-1)是一种与胰岛素原具有高度同源性的、由两种相互作用的多肽激素配体组成的家族成员。IGF-1可影响间充质细胞的迁移、增殖及细胞外基质沉积,因此与纤维化疾病的进展有关。目前,关于槟榔相关口腔黏膜下纤维化(OSF)中IGF-1表达调控的信息有限。本研究旨在比较正常人口腔颊黏膜和OSF标本中IGF-1的表达,并进一步探讨可能导致IGF-1表达上调的潜在机制。采用免疫组织化学方法检测20例OSF标本和10例正常口腔颊黏膜标本。运用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)检测OSF和正常口腔颊黏膜培养细胞中IGF-1的活性。此外,添加槟榔主要生物碱槟榔碱,以探讨可能导致IGF-1表达上调的潜在机制。IGF-1在OSF标本中的表达显著更高(p<0.05),主要由成纤维细胞、内皮细胞及炎性细胞表达。在mRNA和蛋白水平上,OSF中IGF-1蛋白表达均显著高于正常口腔颊黏膜成纤维细胞(BMF)(p<0.05)。此外,还发现槟榔碱能以剂量依赖方式提高IGF-1的mRNA和蛋白表达(p<0.05)。综上所述,本文数据表明,嚼槟榔者的OSF中IGF-1表达显著上调,槟榔碱可能是体内IGF-1表达增强的原因。