Profilin-1在HMGB1/RAGE信号致血栓闭塞性脉管炎大鼠内皮损伤中的作用及机制

项目名称： Profilin-1在HMGB1/RAGE信号致血栓闭塞性脉管炎大鼠内皮损伤中的作用及机制

项目编号： No.81500375

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孔祥骞

作者单位： 山东大学

项目金额： 20万元

中文摘要： 血栓闭塞性脉管炎（TAO）是一种以中小动静脉节段性病变并管腔内血栓形成为特征的炎性疾病，在其发病机制中，内皮细胞发挥“始动性”和“持续性”作用，主要方式为通过介导免疫细胞和炎细胞黏附内皮细胞导致内皮损伤参与血管炎性病变。Profilin-1是一种体内广泛存在的G-肌动蛋白结合蛋白，是内皮损伤过程中的重要因子。我们的前期实验表明Profilin-1参与了TAO发展过程；并且发现HMGB1/RAGE途径是介导TAO内皮损伤的重要上游机制，两者存在共同的下游信号通路。本课题提出HMGB1/RAGE通过Profilin-1调控下游信号，造成内皮损伤的假说。从动物模型和细胞两方面，研究Profilin-1与 HMGB1/RAGE 信号途径中各因子的表达与激活的关系。进一步通过干预 Profilin-1 和RAGE观察对上述通路和病情进展的影响。本课题为明确TAO的发病机制和寻找有效治疗措施提供理论。

中文关键词： 血栓闭塞性脉管炎；前纤维蛋白-1；高迁移率族蛋白B1；晚期糖基化终末产物；血管内皮损伤

英文摘要： Thromboangiitis obliterans (TAO) is a segmental inflammatory disorder that involves primarily the small and medium arteries, veins with thrombosis. In the pathogenesis of TAO, endothelial cells play a key role in initiation and perpetuation of vasculitis lesions through mediating intercellular adhesions between immunocytes as well as inflammatory cells and endothelial cells. Profilin-1, an extensive existing G-actin-binding protein, play a major role in endothelial injury. Our previous experiments show that Profilin-1 involved in the development of TAO, and HMGB1/RAGE pathway is an important upstream signal induced endothelial injury in TAO. Both of them share common downstream signaling pathways. We hypothesize that HMGB1/RAGE regulate downstream signaling through Profilin-1 to induce endothelial injury. To prove the hypothesis, animal models and in vitro model systems will be used in the current study. First we investigate the activation status of Profilin-1 and HMGB1/RAGE signaling pathway. The effects of Profilin-1 on the activation of signaling factors in HMGB1/RAGE pathway will be explored by intervening Profilin-1 and RAGE. Our findings will elucidated the underlying mechanisms of TAO and provide a theoretical basis for effective treatment.

英文关键词： Thromboangiitis Obliterans;Profilin-1;HMGB1;RAGE;endothelial injury