Cellular Signaling and Kidney Function

细胞信号传导和肾功能

• 批准号: 6951813
• 负责人: Douglas C. Eaton
• 金额: $ 134.59万
• 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/6951813
• 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.

尽管多年来对正常肾脏的肾脏细胞生理学进行了研究，但对控制全身动态平衡和相关疾病状态的因素的全面了解仍然不完整。然而，已经非常清楚的是，正常的动态平衡和身体对肾脏病理生理的异常反应涉及各种肾脏过程、全身激素和体内其他组织的反应之间的显著相互作用。虽然其中一些相互作用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新的工具来研究这些相互作用。有细胞和分子生物学方法可以使它 有可能识别和修饰那些负责维持正常体内平衡的蛋白质，以及那些负责肾脏和身体其他部位因肾功能丧失而做出病理生理反应的蛋白质。埃默里大学生理学系和肾病学部在肾脏细胞过程的识别、描述和特征方面有着悠久的研究历史 与正常生理学和病理生理学有关，以及肾脏病理生理学如何影响身体其他组织。这个项目的目标是加强肾脏疾病过程的细胞和分子生物学，并在一个紧密联系的研究小组之间开发新的方向，他们将使用分子和细胞生物学工具来了解肾脏细胞机制中可能导致疾病状态的异常和 这些疾病状态对其他组织的影响。L项目是“ENaC组装、运输、降解和回收”，它将表征肾脏钠通道蛋白表面上独特的细胞加工过程。项目2，“垂垂蛋白在矿质皮质激素--工业高血压中的作用”将研究氯离子在细胞内运动途径的调节。项目3，“酸中毒中的胰岛素信号和肌肉蛋白质代谢”，研究了肌肉的机制。 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研究了肾脏尿素转运蛋白的调节。