MEDIATORS AND EXPRESSION SYSTEMS IN RENAL INJURY

该提案寻求支持，以建立正式的计划项目 致力于急慢性肾脏发病机制的研究 受伤。所述的目标将通过结合 体外与体内方法学1)开发 分子和细胞生物学的多学科策略， 生物化学，超微结构和形态计量学，免疫病理学和 细胞免疫学，以及细胞、器官和整个动物 生理学；以及2)扩展现有的，以及打造新的， 调查人员与不同的人进行了卓有成效的合作 科学背景和兴趣。项目1研究 肾小球内皮细胞和系膜细胞的病理生物学研究 培养；项目2探索肾小球上皮细胞的作用 在体内介导肾小球硬化；项目3检查了 单核/巨噬细胞和其他介质在急性和慢性粒细胞白血病中的作用 实验性肾病综合征慢性肾小球损伤； 项目4试图定义最初和随后的事件 常见病致肾小管细胞损伤的责任 肾毒性药物；项目5探索致病意义 肾脏损伤中第二类MHC抗原的表达；项目6 检测CD8/I类复合体在T细胞功能和功能中的作用 随之而来的杀伤细胞介导的靶向损伤；项目7有两个 主要目标：1)进一步明确改变的肾小球的作用 肾小球发生发展过程中的血流动力学因素 2)探讨肾小球肥大的作用。 液压本身在调和现场观测缺陷中的作用 肾小球膜对大分子的选择性；项目8测试a 涉及先天性总减数的新假说 滤过表面积在系统性红斑狼疮发病机制中的作用 高血压以及进行性肾小球损伤。一小块 要求行政核心提供财政、行政 并为项目参与者提供秘书支持。通过把这个放在 在更大的行政结构下的拟议方案 最近，美国国立卫生研究院资助了哈佛大学肾脏疾病研究中心 (目前仅专注于糖尿病肾脏疾病) 将不需要核心。几乎所有的钱都判给了这个 因此，该计划可用于支持高度 合作研究项目。我们相信这一点 该计划将促进知识获取的加速 关于急性和慢性肾损伤的机制和 从而有助于改进诊断和 肾脏疾病患者的管理。

This proposal seeks support to establish a formal Program Project devoted to the study of mechanisms of acute and chronic renal injury. The stated goals are to be accomplished by combining in vitro with in vivo methodologies 1) to exploit the multidisciplinary strategies of molecular and cell biology, biochemistry, ultrastructure and morphometry, immunopathology and cellular immunology, and cellular, organ and whole animal physiology; and 2) to extend existing, as well as to forge new, fruitful collaborations involving investigators with diverse scientific backgrounds and interests. Project 1 studies the pathobiology of glomerular endothelial and mesangial cells in culture; Project 2 explores the role of glomerular epithelial cells in mediating glomerular sclerosis in vivo; Project 3 examines the roles of monocytes/macrophages and other mediators of acute and chronic glomerular injury in experimental nephrotic syndrome; Project 4 seeks to define the initial and subsequent events responsible for renal tubule cell injury induced by commonplace nephrotoxic drugs; Project 5 explores the pathogenetic significance of class II MHC antigen expression in renal injury; Project 6 examines the role of CD8/class I complexes in T cell function and consequent killer cell-mediated target injury; Project 7 has two major aims: 1) to further define the role of altered glomerular hemodynamic factors in the initiation and progression of glomerular sclerosis; and 2) to explore the role of elevated glomerular hydraulic pressure per se in mediating observed defects in glomerular permselectivity to macromolecules; Project 8 tests a novel hypothesis that implicates congenital reduction in total filtration surface area in the pathogenesis of systemic hypertension as well as progressive glomerular injury. A small Administrative Core is requested to provide fiscal, administrative and secretarial support for program participants. By placing this proposed program under the larger administrative structure of the recently NIH funded Harvard Center for the Study of Kidney Disease (which currently focuses only on diabetic renal disease) additional cores will not be required. Nearly all monies awarded to this program can therefore be utilized for support of the highly collaborative research projects. It is our belief that this program will foster an acceleration in the acquisition of knowledge pertaining to mechanisms of acute and chronic renal injury and thereby contribute to improved strategies for diagnosis and management of patients with renal disease.