牙龈卟啉单胞菌促进牙龈上皮细胞增殖及恶性转化的机制研究

项目名称： 牙龈卟啉单胞菌促进牙龈上皮细胞增殖及恶性转化的机制研究

项目编号： No.81470745

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 潘亚萍

作者单位： 中国医科大学

项目金额： 73万元

中文摘要： 牙龈卟啉单胞菌（P. gingivalis，Pg）为牙周病主要致病菌，Pg侵入牙龈上皮细胞（HGEC）导致牙周感染加重和扩散。本课题组研究显示Pg内化于HGEC，抑制细胞凋亡，促进cyclinD1提前表达和高表达，加快细胞周期进程，促进细胞增殖。通过基因芯片进一步分析发现31个与肿瘤发生相关基因差异性表达。Pg感染牙龈鳞癌细胞可引起c-Fos，c-Jun高表达,特异性荧光标记探针原位杂交检测证实牙龈癌等口腔鳞癌组织中存在Pg。提示上皮细胞中Pg感染可能通过AP-1（c-Fos，c-Jun），提高cyclinD1表达，引发细胞增殖异常，促进上皮细胞恶性转化。通过研究miR-21/PDCD4/JNK/AP-1环路对Pg感染HGEC和牙龈鳞癌细胞cyclinD1的调控作用及芯片筛查等，以期发现Pg促进上皮细胞增殖及恶性转化的分子机制，寻找可能的阻断途径，为口腔肿瘤的预防及治疗提出一条新途径。

中文关键词： 牙龈卟啉单胞菌；慢性牙周炎；牙龈上皮细胞；增殖；恶性转化

英文摘要： Porphyromonas gingivalis(Pg) is the main pathogen of periodontitis. Pg leads to more serious periodontal infection and inflammation by invading immortalized human gingival epithelial cells (HGEC). Our previous studies have showed that internalization of Pg induced infected HGEC in accelerating the process of cell cycle and promoting cell proliferation with early and high expression of cyclin D1. 31 genes associated with tumor occurred different expression by further analyse with microarray. could induce c-Fos and c-Jun increased by internalized gingival carcinoma cell. Pg existed in the gingival carcinoma tissue detected by fluorescence in situ hybridization labeled probe. Epithelial cells infected with Pg possibly improve cyclin D1 expression and promote epithelial cell proliferation and cell malignant transformation through AP-1 (c-Fos, c-Jun). Study the effect of miR-21/PDCD4/JNK/AP-1 signal-regulated network on regulating the expression of cyclin D1 and analysis chip result after Pg internalizing HGEC and gingival squamous carcinoma cell, in order to find molecular mechanisms of Pg promoting proliferation and malignant transformation of HGEC, and look for a new possible blocking way for prevention and treatment of oral carcinoma.

英文关键词： Porphyromonas gingivalis;chronic periodontitis;immortalized human gingival epithelial cells;proliferation;malignant transformation