STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

肾小球通透性的结构决定因素

• 批准号: 6380722
• 负责人: BARBARA S DANIELS
• 金额: $ 19.15万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380722
• 关键词: actins; albumins; angiotensin II; biological transport; clearance rate; confocal scanning microscopy; epithelium; glomerular filtration; glomerulonephritis; hormone regulation /control mechanism; hydrogen peroxide; immunofluorescence technique; insulinlike growth factor; laboratory rat; mathematical model; membrane model; membrane permeability; membrane structure; oxidative stress; renal glomerulus; transmission electron microscopy; vascular endothelium permeability

DESCRIPTION: (Adapted from the applicant's abstract) - This is a revised application for a renewal of a grant to study structural determinants of glomerular permeability. The glomerulus is a complex filter with remarkably high hydraulic conductivity and low macromolecular permeability. Although abnormalities of each of these functions accompany renal disease, the mechanisms by which the filtration barrier is maintained and regulated are not well understood. The investigator proposes to test two central hypotheses: 1. Glomerular permeability is maintained and modulated by cells of the filtration barrier; 2. functional alterations in glomerular epithelial cells can perpetuate or augment abnormalities of the glomerular permeability barrier. Experimental questions address 1) the mechanisms by which hydraulic and macromolecular permeability of the glomerulus is maintained and regulated; the effects of hormones such as ANG II and IGF-1 on permeability, the effects of alterations in cytoskeleton on glomerular permeability and the role of the cytoskeleton in hormones in mediating permeability changes and 2) the role of abnormalities in macromolecular permeability in causing alterations of glomerular epithelial cell function, the effects of albumin exposure on glomerular permeability, and the mechanisms of cellular albumin uptake and oxidant production after exposure to albumin.

描述：（改编自申请人的摘要）- 这是修订版 申请续签赠款以研究结构性决定因素 肾小球通透性。 肾小球是一个复杂的过滤器，具有显着的功能 高导水率和低大分子渗透性。 虽然 这些功能的异常都伴随着肾脏疾病， 维持和调节过滤屏障的机制是 不太理解。 研究者建议测试两个中心 假设： 1. 肾小球通透性由以下因素维持和调节： 过滤屏障的细胞； 2. 肾小球功能改变 上皮细胞可以延续或增强肾小球的异常 渗透性屏障。 实验问题涉及 1) 的机制 肾小球的水力和大分子渗透性是 维护和监管； ANG II 和 IGF-1 等激素的影响 对通透性的影响，细胞骨架的改变对肾小球的影响 渗透性和细胞骨架在激素介导中的作用 通透性变化和2）大分子异常的作用 导致肾小球上皮细胞功能改变的渗透性， 白蛋白暴露对肾小球通透性的影响 暴露后细胞白蛋白摄取和氧化剂产生的机制 至白蛋白。