ERK5在血小板活化和血栓形成中的作用机制研究

细胞外信号调节激酶5（ERK5）是丝裂原蛋白激酶（MAPK）家族中重要的一员，可以被高渗透压、低氧、流体切应力、氧化剂等多种刺激因素激活，与心血管发育和多种临床疾病关系密切。已有研究结果表明，ERK5在血小板中高表达并调控血小板活化。而ERK5调控血小板活化的分子机制、介导ERK5活化的上游信号以及ERK5通路小分子抑制剂的抗栓作用都不清楚。我们将利用多种小分子抑制剂及条件敲除小鼠，结合分子细胞生物学、蛋白质组学、小鼠动脉血栓模型等技术展开深入研究。回答这些关键问题将有助于完善血小板活化调控理论，为临床应用ERK5通路抑制剂作为抗栓药物提供充足的证据。

Extracellular Regulated Protein Kinase 5 (ERK5) is a Mitogen Activated Protein Kinase (MAPK) family member, activated by a variety of stimuli such as high osmotic pressure, hypoxia, fluid shear stress and oxidant, involved in cardiovascular development and some clinical diseases. Recent results suggest that ERK5 is highly expressed in platelets and regulate platelet activation. Based on these findings, we set out to investigate the mechanisms of ERK5 in regulating platelet activation, which upstream signaling activate ERK5, and whether ERK5 signaling pathway play a role in arterial thrombosis. Answering these key questions will enrich the theory of platelet activation, and provide evidence for applying ERK5 pathway inhibitors as antithrombotic agents.