STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

肾小球是一个复杂的过滤器， 导电性和低的大分子渗透性。 异常 水力传导性和大分子渗透性 肾脏疾病的类型，但了解 肾小球通透性屏障的生理学和调节不是 发展良好，可能部分原因是缺乏模型， 肾小球功能可以独立于血流动力学和 荷尔蒙因素，这是重要的，但不是唯一的， 水和大分子穿过肾小球毛细血管的渗透性 墙 两种肾小球通透性体外模型的建立， 肾小球毛细血管壁离散成分的作用 渗透率的维持和调节。 的 分层的、完整的肾小球的过滤特性将在 滤过细胞，而滤过通过单个完整的肾小球， 通过共聚焦显微镜检查毛细血管袢。 此外，本发明还提供了一种方法， 共聚焦显微镜有助于研究细胞内 钙流量和肌动蛋白细胞骨架，介质的渗透性， 在完整肾小球内的离散细胞中。 该提案旨在研究肾小球的功能， 这两种新技术的渗透屏障，共聚焦显微镜 和过滤单元。 这些技术将进一步表征 然后用于开发和扩大可用的均孔和纤维 肾小球大分子通透性的基质模型。 此外，本发明还提供了一种方法， 钙流和肌动蛋白细胞骨架，可能是细胞内介质 将在完整肾小球的离散细胞中检查渗透性 用共聚焦显微镜来确定它们在调节 肾小球通透性 最后，给出了关于 肾小球通透性将应用于两种病理生理模型 与肾小球通透性屏障的急性改变有关。

The glomerulus is a complex filter with remarkably high hydraulic conductivity and low macromolecular permeability. Abnormalities of hydraulic conductivity and macromolecular permeability accompany most types of progressive renal disease, yet the understanding of the physiology and regulation of the glomerular permeability barrier is not well developed, probably due in part to the lack of models where glomerular function can be assessed independently of the hemodynamic and hormonal factors which contribute importantly, but not solely, to the permeance of water and macromolecules across the glomerular capillary wall. The development of two in vitro models of glomerular permeability whereby the contribution of discrete components of the glomerular capillary wall to the maintenance and regulation of permeability can be analyzed. The filtration properties of layered, intact glomeruli will be assessed in a filtration cell while the filtration across single, intact, glomerular capillary loops will be examined by confocal microscopy. In addition, confocal microscopy facilitates the investigation of intracellular calcium flux and the actin cytoskeleton, mediators of permeability in other organs, in discrete cells within intact glomeruli. This proposal is designed to investigate the function of the glomerular permeability barrier with these two novel techniques, confocal microscopy and the filtration cell. The techniques will be further characterized and then utilized to develop and expand the available isoporous and fiber matrix models of glomerular macromolecule permeability. In addition, calcium flux and the actin cytoskeleton, likely intracellular mediators of permeability, will be examined in discrete cells in intact glomeruli with confocal microscopy to determine their role in the modulation of glomerular permeability. Finally, the resultant concepts about the glomerular permeability will be applied to two pathophysiologic models associated with acute alterations in the glomerular permeability barrier.