CELL AND MOLECULAR PATHOBIOLOGY OF RENAL DISEASE

这项修订后的申请寻求对一项广泛计划的持续支持 肾脏研究旨在了解细胞和分子 肾脏疾病的机制。调查人员将研究细胞 和包括内皮细胞在内的肾脏的分子病理生物学 肾微血管分化与细胞骨架调控 肾上皮细胞膜蛋白的组织和极性 在体内，分子的结构和组装的定义 肾刷边缘。这些问题将主要在肾脏方面解决。 细胞培养系统，包括原代和早期传代培养 内皮细胞、肾上皮细胞和已建立的细胞系 如MDCK、LLCPK等细胞。此外，该菌株的表型 肾上皮细胞细胞骨架的特定功能缺陷或 它的细胞黏附特性将在转基因小鼠身上进行检测。 形态、生化、免疫化学、细胞生物学和分子 生物技术将被用来研究这些问题。核心 包括中央成像核心在内的设施将为该集团提供支持 研究工作，并作为广泛协作的重点 学习。 这些研究项目的目的是评估 肾细胞和基质的性质及这些成分的作用 可能计划改变结构和功能，与各种 各种形式的肾脏疾病，从而为 合理防治。

This revised application seeks continued support for a broad program in renal research directed at understanding the cellular and molecular mechanisms of renal disease. The investigators will study the cellular and molecular pathobiology of the kidney including endothelial cell differentiation of renal microvasculature, the regulation of cytoskeletal organization and polarity of membrane proteins in renal epithelial cells in vivo, the definition of the molecular architecture and assembly of the renal brush border. These problems will be addressed primarily in renal cell culture systems, including primary and early passage cultures of endothelial cells, renal epithelial cells, and in established cell lines such as the MDCK, and LLCPK, cells. In addition, the phenotype of specific functional defects in the renal epithelial cell cytoskeleton or it's cell adhesion properties will be examined in transgenic mice. Morphological, biochemical, immunochemical, cell biological and molecular biological techniques will be used to investigate these problems. core facilities including a central imaging core will support the group research effort, and serve as a focus for a wide range of collaborative studies. The research projects are directed at an evaluation of the fundamental properties of renal cells and matrix and the role that these components may plan int he altered structure and function associated with various forms of renal disease and thus provide a base of knowledge for a rational approach to prevention and treatment.