BIOLOGY OF CHILDHOOD NEPHROTIC SYNDROME

该申请寻求继续资助一个互动小组， 临床和基础科学家致力于研究 儿童肾病综合征及其密切相关疾病， 目的明确特定基因的致病作用 产品，并确定其后遗症在肾损伤。 认识 肾素-血管紧张素系统（RAS）在这些 抑制剂的治疗效果所反映的环境 动物和/或人类RAS的组成部分，我们也认为 采用遗传学方法定义RAS的明显优势 具体缴款组成部分及其参与方式 肾组织损伤 项目0001将定义肾小球硬化症的生物学事件 依赖于血管紧张素II（Ang II）和不依赖于血管紧张素II（Ang II）。 为此，DNA重组小鼠与“区域”血管紧张素 将使用本中心开发的受体基因敲除。 项目0004将研究基因变异的意义， 肾功能进行性丧失的RASE 阻塞性/反流性肾病。 该项目将扩大到 测定ACE基因活性的功能意义， 通过检查人类基因组和DNA的局部组织损伤 重组小鼠模型。 越来越多的证据表明 表明血管紧张素Ⅱ通过血管紧张素Ⅱ发挥重要作用 2型受体（AT 2）。 与之相比， RA的下游步骤，在其 由于缺乏实验工具，监管作用。 基于 我们的肾素敲除研究项目0005的结果令人鼓舞 提出了一系列的实验，以确定的作用， 肾组织重塑过程中的肾素失调。

The application seeks continued funding for an interactive team of clinical and basic scientists dedicated to the investigation of childhood nephrotic syndrome and closely related diseases, with the objective of identifying the pathogenic role of specific gene products and defining their sequelae in renal injury. Recognizing the significance of the renin-angiotensin system (RAS) in these settings as reflected by the therapeutic effectiveness of inhibitors of the components of RAS in animals and/or humans, we also perceive the clear advantage of taking genetic approaches in defining RAS's specific contributory components and their mode of participation in renal tissue injury. Project 0001 will define the biological events in glomerulosclerosis that are dependent upon vs. independent of angiotensin II (Ang II). For this purpose, DNA recombinant mice with 'regional' Ang receptor gene knock-out developed in our Center will be used. Project 0004 will examine the significance of gene variants within RASE for the progressive loss of renal function in obstructive/reflux nephrophath. The PROJECT will expand into determination of the functional significance of ACE gene activity in local tissue injury by examining human genome and a DNA recombinant mouse model. There is growing body of evidence to indicate that Ang II exerts significant functions through ANG II type 2 receptor (AT2) in the kidney. Renin, in contrast to more downstream steps of RAs, has not been well studied in terms of its regulatory role due to the lack of experimental tools. Based on the encouraging results of our renin knock-out study, Project 0005 proposes a series of experiments for defining the role of disregulation of renin in the renal tissue remodeling process.