Cellular Signaling and Kidney Function

细胞信号传导和肾功能

• 批准号: 7850092
• 负责人: Douglas C. Eaton
• 金额: $ 2.98万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850092
• 关键词: Cellular; Signaling; Kidney; Function

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 1 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 Mineralocorticoid-Induced 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.

尽管对正常肾脏的肾细胞生理学进行了多年的研究，但综合 了解控制全身稳态平衡和相关疾病状态的因素 仍然不完整。然而，已经非常清楚的是，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以下因素之间的显着相互作用： 各种肾脏过程、全身激素以及体内其他组织的反应。 尽管其中一些相互作用已经为人所知一段时间了，但其分子机制 直到最近才对驱动细胞凋亡和增殖反应等其他反应进行研究。这 主要是因为现在可以使用新工具来研究这些相互作用。有蜂窝 和分子生物学方法，使识别和修饰蛋白质成为可能 负责维持正常的体内平衡和那些负责 肾内和身体其他部位对肾功能丧失的病理生理反应 功能。埃默里大学生理学系和肾脏病学部拥有悠久的历史 细胞过程的识别、描述和表征的研究历史 肾脏与正常生理和病理生理相关，以及肾脏病理生理如何影响 影响身体的其他组织。该项目的目标，肾脏细胞和分子生物学 疾病过程，是为了加强疾病之间现有的相互作用并开发新的方向 紧密结合的研究人员小组，他们将使用分子和细胞生物学工具来理解 可能导致疾病状态的肾细胞机制畸变及其影响 其他组织的疾病状态。项目1是“ENaC组装、贩运、降解和回收” 这将表征肾钠通道蛋白明显独特的细胞加工过程。 项目 2“Pendrin 在盐皮质激素诱发的高血压中的作用”将研究 CCD 中氯离子移动的途径。项目 3，“胰岛素信号传导和肌肉蛋白质周转 在《酸中毒》中，研究了与肾脏疾病相关的肌肉萎缩机制。最后， 项目4，“MDCK细胞中尿素转运蛋白的调节”，检查肾尿素的调节 在新模型系统中运输蛋白质。