Analysis of PECAM-1-dependent mechanotransduction in endothelial cells

内皮细胞中 PECAM-1 依赖性机械转导的分析

• 批准号: 54658571
• 负责人: Professor Dr. Carsten Grashoff
• 金额: --
• 依托单位: Institut für Integrative Zellbiologie und Physiologie (IIZP)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/54658571?language=en
• 关键词: Analysis; PECAM; dependent; mechanotransduction; endothelial

Physical stress contributes to many diseases such as atherosclerosis. However, the molecular mechanisms of cellular mechanotransduction, the process by which cells sense and respond to mechanical signals, are still largely unknown. Atherosclerotic plaques occur preferentially in regions of low, disturbed blood flow at sites of vessel branching or curvature. The complex blood flow in these areas stimulates inflammatory signalling pathways in endothelial cells, which initiate atherogenesis. PECAM-1 was recently identified as a mechanoresponsive protein that is essential for the sensing and transmission of shear forces and hence was implicated in the initiation of atherosclerosis. Here, I propose to investigate the molecular mechanism of PECAM-1- dependent mechanotransduction. I will examine effects of mutations in PECAM-1 on cellular responses to fluid shear stress. Based on these results, the role of the implicated effector molecules will be further analyzed. Finally, I will investigate direct force transduction by PECAM-1 using stretchable substrates or magnetic beads.

身体压力导致许多疾病，如动脉粥样硬化。然而，细胞机械转导的分子机制，即细胞感知和响应机械信号的过程，在很大程度上仍然未知。动脉粥样硬化斑块优先发生在血管分支或弯曲部位的低血流干扰区域。这些区域的复杂血流刺激内皮细胞中的炎症信号通路，从而引发动脉粥样硬化形成。PECAM-1最近被鉴定为机械应答蛋白，其对于剪切力的感测和传递是必不可少的，因此与动脉粥样硬化的起始有关。在这里，我建议研究PECAM-1依赖性机械转导的分子机制。我将研究PECAM-1突变对细胞对流体剪切应力反应的影响。基于这些结果，将进一步分析涉及的效应分子的作用。最后，我将研究直接力转导PECAM-1使用可拉伸基板或磁珠。