STRUCTURAL DETERMINANTS OF GLOMERULAR PERMEABILITY

描述：(改编自申请人的摘要)-这是一个修订后的 申请续期补助金以研究结构决定因素 肾小球通透性。肾小球是一个复杂的滤器，具有显著的 高导水性和低大分子渗透性。虽然 这些功能的每一种异常都伴随着肾脏疾病， 维持和调节过滤屏障的机制有 不是很清楚。调查员提议测试两个中心 假设：1.肾小球通透性的维持和调节 滤过屏障细胞；2.肾小球功能改变 上皮细胞可使肾小球的异常持续或增大。 渗透性屏障。实验问题解决了1)机制通过 肾小球的水力渗透性和大分子渗透性是什么 维持和调节；血管紧张素Ⅱ和胰岛素样生长因子-1等激素的作用 肾小球细胞骨架改变对通透性的影响 通透性与细胞骨架在激素调节中的作用 通透性变化和2)大分子异常的作用 通透性导致肾小球上皮细胞功能改变， 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 到白蛋白。

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.