Cellular Signaling and Kidney Function

细胞信号传导和肾功能

• 批准号: 7098737
• 负责人: Douglas C. Eaton
• 金额: $ 131.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098737
• 关键词: biological signal transduction; biological transport; kidney function; pathologic process

Despite years of research on renal cell physiology in the normal kidney, a comprehensive understanding of the factors that govern total body homeostatic balance and associated disease states is still incomplete. However, it has become quite clear that normal homeostatic balance and the abnormal responses of the body to renal pathophysiology involves significant interaction among a variety of renal processes, systemic hormones, and responses of other tissues within the body. Although some of these interactions have been known for some time, the molecular mechanisms driving others such as apoptotic and proliferative responses have only recently been investigated. This is primarily because of new tools which are now available to study these interactions. There are cellular and molecular biological methods that make it possible to identify and modify the proteins that are responsible for maintaining normal homeostatic balance and those which are responsible for pathophysiological responses within the kidney and elsewhere in the body in response to loss of renal function. The Department of Physiology and the Division of Nephrology at Emory University have a long history of research into the identification, description and characterization of cellular processes in the kidney that are related to normal physiology and pathophysiology and how renal pathophysiology can impact other tissues in the body. The objective of this Program, Cellular and Molecular Biology of Renal Disease Processes, is to reinforce the existing interactions and develop new directions between a closely knit group of investigators who will use molecular and cellular biological tools to understand aberrations in renal cellular mechanisms that can lead to disease states and the impact of these disease states on other tissues. Project l is "ENaC Assembly, Trafficking, Degradation, and Recycling" which will characterize the apparently unique cellular processing of renal sodium channel proteins. Project 2, "The Role of Pendrin in Mineralocortieoid-Indueed Hypertension" will examine regulation of a pathway for chloride movement in the CCD. Project 3, "Insulin Signaling and Muscle Protein Turnover in Acidosis", examines the mechanisms of muscle wasting associated with renal disease. The last, Project 4, "Regulation of Urea Transporters in MDCK Cells", examines the regulation of renal urea transport proteins in a new model system.

尽管对正常肾脏中的肾细胞生理学进行了多年的研究，但对支配全身稳态平衡和相关疾病状态的因素的全面理解仍然不完整。然而，已经变得相当清楚的是，正常的稳态平衡和身体对肾脏病理生理学的异常反应涉及各种肾脏过程、全身激素和身体内其他组织的反应之间的显著相互作用。虽然这些相互作用中的一些已经知道了一段时间，但驱动其他相互作用的分子机制，如凋亡和增殖反应，直到最近才被研究。这主要是因为现在有了研究这些相互作用的新工具。有细胞和分子生物学方法可以使其成为 有可能鉴定和修饰负责维持正常稳态平衡的蛋白质以及负责响应于肾功能丧失的肾内和身体其他部位的病理生理学反应的蛋白质。埃默里大学的生理学系和肾脏学系在肾脏细胞过程的鉴定、描述和表征方面有着悠久的研究历史， 与正常生理学和病理生理学以及肾脏病理生理学如何影响体内其他组织相关。该计划的目标，肾脏疾病过程的细胞和分子生物学，是加强现有的相互作用，并开发一个紧密联系的研究小组之间的新方向，他们将使用分子和细胞生物学工具来了解可能导致疾病状态的肾细胞机制畸变， 这些疾病状态对其他组织的影响。项目1是“ENaC组装、运输、降解和回收”，其将表征肾钠通道蛋白的明显独特的细胞加工。项目2，“Pendrin在矿物质皮质激素诱导的高血压中的作用”将研究CCD中氯离子运动途径的调节。项目3，“胰岛素信号和肌肉蛋白质周转酸中毒”，检查肌肉的机制， 与肾脏疾病相关的消瘦。最后，项目4，“MDCK细胞中尿素转运蛋白的调节”，在一个新的模型系统中检查肾尿素转运蛋白的调节。