Chung-Hung Tsai, Shun-Fa Yang, Yu-Chao Chang
Department of Oral Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Oral Oncol. 2007 Aug;43(7):680-5. doi: 10.1016/j.oraloncology.2006.08.009. Epub 2006 Oct 25.
Cystatin C is a 13kDa non-glycosylated basic protein belonging to cystatin family. It is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare cystatin C expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of cystatin C expression. Twenty-five OSF specimens and six of normal buccal mucosa were examined by immunohistochemistry. The activity of cystatin C from fibroblasts cultured from OSF and normal buccal mucosa were evaluated by using reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Furthermore, the effect of arecoline, the major areca nut alkaloid, was explored. Cystatin C expression was significantly higher in OSF specimens (p<0.05) and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. OSF demonstrated significantly higher cystatin C expression than normal buccal mucosa fibroblasts both in mRNA and protein levels (p<0.05). In addition, arecoline was also found to elevate cystatin C mRNA and protein expression in a dose-dependent manner (p<0.05). Taken together, the data demonstrate that cystatin C expression is significantly upregulated in OSF from areca quid chewers and arecoline may be responsible for the enhanced cystatin C expression in vivo.
胱抑素C是一种13kDa的非糖基化碱性蛋白，属于胱抑素家族。它在多种纤维化疾病中持续且显著上调。本研究的目的是比较胱抑素C在正常人颊黏膜和口腔黏膜下纤维化（OSF）标本中的表达，并进一步探讨可能导致胱抑素C表达诱导的潜在机制。通过免疫组织化学检查了25个OSF标本和6个正常颊黏膜标本。使用逆转录聚合酶链反应和酶联免疫吸附测定法评估了从OSF和正常颊黏膜培养的成纤维细胞中胱抑素C的活性。此外，还探讨了槟榔的主要生物碱槟榔碱的作用。胱抑素C在OSF标本中的表达明显更高（p<0.05），主要由成纤维细胞、内皮细胞和炎症细胞表达。OSF在mRNA和蛋白质水平上均显示出比正常颊黏膜成纤维细胞更高的胱抑素C表达（p<0.05）。此外，还发现槟榔碱以剂量依赖的方式提高胱抑素C的mRNA和蛋白质表达（p<0.05）。综上所述，数据表明，咀嚼槟榔者的OSF中胱抑素C表达明显上调，槟榔碱可能是体内胱抑素C表达增强的原因。
