RENAL RESPONSE TO INJURY

乔治·M·奥布莱恩肾脏研究中心的续签申请 在华盛顿大学的研究重点是肾脏对 几种形式的损伤，目的是澄清为什么肾脏疾病 决心或进步。该中心由5个科学项目和 2个核心，汇集了3名基础科学家和4名肾脏科学家 4个独立的部门。这些研究建议集中在3个分子上。 肾脏损伤反应的重要性：细胞周期调节 蛋白质、骨桥蛋白和SPARC及其基础、应用和临床研究 每一主题的提出。在项目1中，罗伯茨博士将探索 调控细胞生长的几种细胞周期蛋白，以及在项目2中 Shankland博士将扩展这些观察以确定细胞周期蛋白的作用 激酶抑制剂在肾小球上皮细胞肥大中的作用 在体外和体内对各种刺激做出反应。在项目3中，Dr。 贾切利将继续研究骨桥蛋白是一种 间质炎症/纤维化集中于与转化生长因子β的相互作用， 在项目4中，约翰逊博士将探索初始 肾小管间质损伤可导致盐依赖型高血压。在项目中 Sage博士将评估SPARC调节TGFbeta的机制 和肾小球系膜细胞和上皮细胞产生胶原，以及 Couser博士将利用SPARC基因敲除和转基因小鼠来定义 SPARC在体内肾小球和间质性肾脏疾病中的作用全 五个项目将继续研究细胞周期调节蛋白， 骨桥蛋白和SPARC在人类肾脏疾病中的作用据预计， 在基础、应用和临床层面提出的研究将推动 了解肾脏对损伤的反应及其后果。

This renewal application for the George M. O' Brien Kidney Research Center at the University of Washington focuses on the response of the kidney to several forms of injury with the goal of clarifying why renal diseases resolve or progress. The Center is composed of 5 scientific projects and 2 cores that bring together 3 basic scientists and 4 renal scientists from 4 separate departments. The studies proposed focus on 3 molecules of importance in the renal response to injury: cell cycle regulatory proteins, osteopontin and SPARC, with basic, applied and clinical studies proposed of each topic. In Project 1, Dr. Roberts will explore the role of several cell cycle proteins in regulatory cell growth, and in Project 2 Dr. Shankland will extend these observations to define the role of cyclin kinase inhibitors in causing hypertrophy of the glomerular epithelial cell in response to various stimuli in vitro and in vivo. In Project 3, Dr. Giachelli will continue studies of osteopontin is a mediator of interstitial inflammation/fibrosis focussing on interactions with TGFbeta, and in Project 4 Dr. Johnson will explore the mechanisms by which initial tubulointerstitial injury leads to salt-dependent hypertension. In Project 3, Dr. Sage will assess the mechanisms by which SPARC regulates TGFbeta and collagen production by glomerular mesangial and epithelial cells, and Dr. Couser will utilize SPARC knock-out and transgenic mice to define the role of SPARC in glomerular and interstitial renal disease in vivo. All five projects will pursue studies of cell cycle regulatory proteins, osteopontin and SPARC in human renal disease. It is anticipated that the studies proposed at basic, applied and clinical levels will advance the understanding of the renal response to injury and its consequences.