Wnt/β-catenin信号对巨噬细胞抗结核分枝杆菌感染过程中细胞凋亡与坏死的调控机制研究

项目名称： Wnt/β-catenin信号对巨噬细胞抗结核分枝杆菌感染过程中细胞凋亡与坏死的调控机制研究

项目编号： No.31460301

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 吴晓玲

作者单位： 宁夏大学

项目金额： 50万元

中文摘要： 巨噬细胞作为结核分枝杆菌的宿主细胞和靶细胞，它与结核分枝杆菌相互作用后发生的凋亡与坏死对结核病的发生、发展及预后具有重要影响。但是，由于其相互作用过程涉及的信号通路十分复杂，其调控机制尚未阐明。近年研究表明，Wnt/β-catenin信号通过调控宿主细胞的凋亡参与多种疾病的发生发展过程。但其对结核结核分枝杆菌感染后巨噬细胞的凋亡与坏死调控尚未见相关报道。 基于以上研究背景，本研究首先采用Wnt3a条件培养基和DKK1处理结核分枝杆菌感染后的小鼠巨噬细胞，探讨Wnt/β-catenin信号通路对巨噬细胞凋亡与坏死的调控作用；进而用caspase抑制剂和RNAi技术分别抑制和沉默凋亡与坏死通路相关基因，阐明Wnt/β-catenin参与调控凋亡和坏死的途径，研究将揭示Wnt/β-catenin信号对巨噬细胞命运的调控机制，并为结核病的预防及靶向药物研制提供理论依据。

中文关键词： Wnt/β-catenin信号；结核分枝杆菌；细胞凋亡；细胞坏死

英文摘要： Macrophage is host cell as well as target cell of Mycobacterium tuberculosis (Mtb). The apoptosis and necrosis of macrophage post infection with Mtb has an important impact on the pathogenesis and outcome of tuberculosis. However, due to the complex signaling pathways involved in this biological process , the mechanism has not been well elucidated. Emerging evidence shows that Wnt/β-catenin signal involved in pathogenesis of diverse diseases through regulating apoptosis of target cell. Whether Wnt/β-catenin signal is involved in regulating the apoptosis and necrosis of macrophage infected with Mtb remains unknown. In the present study, firstely, we explored the regulation of Wnt/β-catenin signaling pathway on the apoptosis and necrosis of macrophage treated with Wnt3a conditioned medium (CM) and DKK1 with infection of Mtb. Then, caspase inhibitor was employed to examine whether the caspase-dependent mechanism was involved in the Wnt3a promoted cell apoptosis. And RNAi vector was employed to examine the necrosis pathway regulated by Wnt3a. and Our datas will reveal the mechanism of Wnt/β-catenin signal on the fate of the macrophages , Our work will provide a new insight into the theory basis for development of targeted drugs of tuberculosis .

英文关键词： Wnt/β-catenin signal;Mycobacterium tuberculosis;apoptosis;necrosis