项目名称: 组蛋白去甲基化酶KDM5B在巨噬细胞极化和闭塞性细支气管炎发生中的调控机制研究
项目编号: No.31200678
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 免疫学
项目作者: 李静
作者单位: 同济大学
项目金额: 25万元
中文摘要: 闭塞性细支气管炎是影响肺移植后发病率和致死率高的主要原因。目前有研究表明巨噬细胞在OB发生中起重要的作用,但关于巨噬细胞与OB发生的关系还知之甚少。本项目利用巨噬细胞的效应细胞形式M1和M2巨噬细胞,筛选表观遗传学的调控因子组蛋白去甲基化酶。发现组蛋白去甲基化酶KDM5B在M1和M2巨噬细胞表达呈现明显差异。并且KDM5B表达改变出现在M1和M2巨噬细胞标记基因改变前。因此本项目将基于这些基础,进一步证实KDM5B与M1和M2巨噬细胞极化的关系,并探讨其调控机制。并利用建立KDM5B的基因敲除小鼠,观察该基因与OB发生的关系,从而进一步阐述OB发生的分子机制。这些原创性工作不仅具有重要的理论意义,对临床OB的诊断和治疗有关键的指导作用。
中文关键词: 巨噬细胞;极化;KDM5B;OB;STAT3
英文摘要: Obliterative bronchiolitis (OB) is the leading cause of morbidity and death after lung transplantation. It has been reported that macrophage plays a crucial role in OB development. While the relationships between macrophage and OB development are poorly understood. Our project use effector cell types of macrophage-M1 and M2 macrophages as experiment material, and screened epigentics regulation factor-histone demethylase. We find histone demethylase KDM5B expressing levels obviously different in M1 and M2 macrophage. And the expressing levels changes of KDM5B ahead of M1 and M2 marker genes. Base on these findings, we will further comfirm the relationship between KDM5B and M1 amd M2 polarization, and investigate the regulation mechanism. Through establishing KDM5B knock-out mice, we will observe the relationship between KDM5B and OB development, and further explain the molecular mechanism of OB development. These original research not only show a significant theoretical importance, but also show a pivotal function in directing OB clinical diagnosis and treatment.
英文关键词: macrophage;polarization;KDM5B;OB;STAT3