Decoding gap junction communication under shear stress

解码剪切应力下的间隙连接通讯

• 批准号: 7268787
• 负责人: Mia M Thi
• 金额: $ 2.09万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-25 至 2008-01-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268787
• 关键词: Decoding; gap; junction; communication; under

DESCRIPTION (provided by applicant): In the endothelium very little is known about the mechanisms that are involved in regulating cellular signaling via gap junctions in response to hemodynamic shearing forces. Relatively few studies have investigated the expression and function of individual gap junction proteins in response to flow-induced fluid shear stress. Although nitric oxide (NO) has been shown to modulate the gap junction communication in static cell culture, the regulation of shear induced NO on this communication has not yet been explored. The question of how this autacoid release regulates different connexins in the various hemodynamic schemes (laminar or disturbed) needs to be investigated. In addition, the question of how fluid shear stress affects intercellular communication in the absence of cytoskeleton also needs to be studied, since cytoskeletal proteins are speculated to be involved in gap junction assembly. The strategy outlined in this proposal will allow us to elucidate the poorly understood physiological regulatory mechanisms of gap junctions in the endothelium during vessel wall remodeling in response to various hemodynamic shearing forces using newly developed techniques such as siRNA and Long Oligo microarrays.

描述（由申请人提供）：在内皮中，对通过间隙连接调节细胞信号传导以响应血流动力学剪切力的机制知之甚少。相对较少的研究已经调查的表达和功能的个别间隙连接蛋白的流动诱导的流体剪切应力。虽然一氧化氮（NO）已被证明可以调节静态细胞培养中的差距连接通讯，但剪切诱导的NO对这种通讯的调节尚未被探索。这种autacoid释放如何调节不同的连接蛋白在各种血流动力学计划（层流或干扰）的问题需要研究。此外，流体剪切应力如何影响细胞间通讯的情况下，细胞骨架的问题也需要研究，因为细胞骨架蛋白被推测参与间隙连接组装。在这项建议中概述的策略将使我们能够阐明在血管壁重塑过程中，响应于各种血流动力学剪切力，使用新开发的技术，如siRNA和长寡核苷酸微阵列的内皮细胞间隙连接的生理调节机制知之甚少。