NF-kappaB-miR-30a-SOCS-3反馈环路在尼古丁促吸烟相关性牙周炎牙周组织炎性损伤中的作用及机制研究

项目名称： NF-kappaB-miR-30a-SOCS-3反馈环路在尼古丁促吸烟相关性牙周炎牙周组织炎性损伤中的作用及机制研究

项目编号： No.81470743

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： 王小竞

作者单位： 中国人民解放军第四军医大学

项目金额： 73万元

中文摘要： 牙周炎严重危害口腔健康，吸烟与牙周炎密切相关但机制不明。我们前期首次证实牙周膜细胞存在烟碱型乙酰胆碱受体α7亚型（α7 nAChR）功能性表达，且尼古丁可通过该受体激活ERK/STAT3/NF-κB等信号通路，加重牙周组织破坏。预实验证实，尼古丁可上调mir-30a表达，生物信息学预测其启动子区存在多个NF-κB结合位点，而mir-30a靶基因SOCS-3可能通过STAT3影响NF-κB活化。由此推测，尼古丁激活α7 nAChR后，可通过NF-κB-mir-30a-SOCS-3环路参与牙周炎发病进程。本项目拟以牙周炎大鼠、局部干扰α7 nAChR表达和局部干扰/过表达mir-30a的大鼠及其对应的牙周膜细胞为研究模型，从分子、细胞和组织等多种水平系统探讨NF-κB-mir-30a-SOCS-3环路在吸烟相关性牙周炎牙周组织炎性损伤中的作用及机制。为吸烟相关性牙周炎的防治提供新的理论依据。

中文关键词： 核因子-κB；微小RNA-30a；细胞因子信号传导抑制因子-3；烟碱型乙酰胆碱受体α7亚型；牙周膜细胞

英文摘要： Periodontitis, which is the main reason for tooth loss, is one of the most common chronic oral diseases in adults. Numerous data demonstrated that smoking is one of the major risk factors for periodontitis. However, the mechanisms behind the effects of smoking on periodontal destruction are still not well understood. Our previous studies demonstrated the functional expression of α7 nAChR in periodontal ligament cells (PDLC). Nicotine could induce periodontium destruction through activation of signal pathways, such as ERK1/2, STAT3 and NF-κB, mediated by α7 nAChR. In our previous research, nicotine coud upregulate expression of mir-30a in PDLC. It is predicated that the promoter of mir-30a has several NF-κB binding points through bioinformatics. In addition, SOCS-3, the target gene of mir-30a, can regulate expression of NF-κB through supressing expression of STAT3. All these results indicating that nicotine could affect the inflammatory process of periodontium through NF-κB-mir-30a-SOCS-3 feedback loop . This study is designed to investigate the inflammatory process of PDLC and periodontium under the circumstance with the affection of normal/nicotine/α7 nAChR siRNA/mir-30a mimics and inhibitor/mir-30a agomir and antagomir, thus to explore the detailed mechanism of NF-κB-mir-30a-SOCS-3 in the inflammatory process of periodontium in smoking- associated periodontitis. We aim to provide a better theoretical basis for preventing and treating the smoking- associated periodontitis.

英文关键词： NF-kappaB;miR-30a;SOCS-3;α7 nAChR;periodontal ligament cells