PERICYTE CONTRACTILITY AND MICROVASCULAR PERMEABILITY

周细胞收缩性和微血管渗透性

• 批准号: 2224636
• 负责人: DAVID SHEPRO
• 金额: $ 21.99万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2224636
• 关键词: biomarker; cytoskeletal proteins; electrofocusing; gel electrophoresis; gene expression; muscle relaxation; phosphorylation; second messengers; tissue /cell culture; vascular endothelium permeability; vascular smooth muscle; western blottings

In the microvasculature, endothelial cells are the primary physical barrier between blood and tissues. The other microvessel wall cell is the pericyte. Although much has been learned about the biology of endothelium, appreciably less is known about pericytes. The focus of this study is to demonstrate the: phenotypic expression of specific contractile proteins in pericytes from different microvascular beds; the mechanisms by which pericytes contract and relax; pericyte humoral com- munication with endothelial cells; finally, to correlate these structural, biochemical and physiological characteristics and changes in interendothelial junctional permeability. The experimental protocols involve the culture of pericytes, and when applicable, their coculture with homologous endothelial cells obtained from bovine retina, lung, and adrenal tissues. This sample of tissues reflects microvascular beds with significant degrees of differences in permeability and different pericyte to endothelial ratios. High priority is given to the identity of specific biochemical markers and physiological properties that are related to pericyte contraction, and that may distinguish them from endothelial and vascular smooth muscle cells. Pericyte phenotypes are also thought to be associated with basal inherent microvascular permeabilities as seen in different organs and tissues. Another priority is to demonstrate in the paracrine communication pathways between pericytes and endothelial cells the importance of prostanoids and other agonists that are known to modulate barrier function and to contract or relax one or both cell types. In these experiments, pericytes and en- dothelial cells will be co-cultured to measure cell to cell signaling and pericyte influence on the differentiation of the endothelial junctional cytoskeletal contractile proteins in relationship to macromolecule transport. Pericytes will be cultured on a silicone substrate and silicone deformation will indicate contraction. The second messenger pathway that regulates pericyte contractile protein phosphorylations will be identified. All of the quantitative techniques and culture procedures associated with these goals are routinely performed in the laboratory and have been published.

在微脉管系统中，内皮细胞是主要物理 血液和组织之间的障碍。 另一个微血管壁细胞是 周围。 尽管已经了解了很多有关的生物学 内皮，对周细胞的了解少。 重点 这项研究是为了证明：特定的表型表达 来自不同微血管床周细胞中的收缩蛋白；这 周细胞收缩和放松的机制；周围的体液com- 用内皮细胞进行通讯；最后，将这些关联 结构，生化和生理特征以及变化 间皮间接口通透性。 实验方案 涉及周细胞的培养 从牛视网膜，肺和 肾上腺组织。 该组织样本反映了微血管床 渗透率和不同周细胞的显着程度 到内皮比。 优先考虑的身份 特定的生化标记和生理特性 与周细胞收缩有关，这可能会将其与众不同 内皮和血管平滑肌细胞。 周细胞表型是 也被认为与基础固有的微血管有关 在不同的器官和组织中看到的渗透率。 另一个优先事项 是在旁分泌通信途径中演示 周细胞和内皮细胞前列腺素和其他 已知会调节屏障功能并收缩或 放松一种或两种细胞类型。 在这些实验中，周细胞和en- 多皮细胞将共培养以测量细胞对细胞信号的传导和 周细胞对内皮连接的差异的影响 与大分子关系的细胞骨架收缩蛋白 运输。 周细胞将在硅树底物上培养，并 有机硅变形将表明收缩。 第二使者 调节周细胞收缩蛋白磷酸化的途径将 被识别。 所有定量技术和文化程序 与这些目标相关的 已出版。