STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

描述：（改编自申请人的摘要）-这是一个修订版 申请续发研究资助金，以研究 肾小球通透性 肾小球是一个复杂的过滤器， 高导水率和低大分子渗透性。 虽然 这些功能中的每一个的异常都伴随着肾脏疾病， 维持和调节过滤屏障的机制是 没有很好地理解。 研究者建议测试两个中心 假设：1. 肾小球通透性的维持和调节是由 过滤屏障的细胞; 2. 肾小球功能改变 上皮细胞可以使肾小球的异常永久存在或增强， 渗透屏障 实验问题解决1）机制， 肾小球的液压和大分子渗透性是 维持和调节;激素如ANG II和IGF-1的作用 细胞骨架改变对肾小球通透性的影响， 细胞骨架在激素介导的 渗透性变化和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 白蛋白。

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.