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Cell Cycle and Podocyte Apoptosis

细胞周期和足细胞凋亡

基本信息

批准号：
7921100
负责人：
Stuart James Shankland
金额：
$ 8.58万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-21 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7921100
关键词：
Abbreviations Apoptosis Apoptotic Applications Grants Basement membrane Binding Cell Culture System Cell Cycle Cell Cycle Proteins Cell Cycle Regulation Cell Nucleus Cell Proliferation Cell physiology Cells Cessation of life Clinical Complex Cyclin-Dependent Kinases Cyclins Data Development Diabetes Mellitus Diabetic Nephropathy Disease Epidemic Experimental Models Fibroblasts Filtration Funding Generations Goals Grant Immunoprecipitation In Vitro Injury Kidney Kidney Diseases Kidney Failure Location Mus Nuclear Phosphotransferases Proliferating Proteins Proteinuria Recruitment Activity Regulation Renal function Renal glomerular disease Reporting Research Role Specialized Epithelial Cell Testing Time Tubular formation Urine cyclin I diabetic glomerular filtration glomerulosclerosis in vivo inhibitor/antagonist injured mesangial cell non-diabetic novel podocyte prevent scaffold

项目摘要

DESCRIPTION (provided by applicant): Kidney disease is increasing at epidemic rates in the US. One clinical sign of kidney disease is protein in the urine (proteinuria). This is typically due to a leak in the normal filtration barrier, and in part is due to injury to a cell called the podocyte. Podocytes are specialized cells that function to limit proteinuria. However, in many diseases including diabetes, podocytes are injured to the point of death, referred to as apoptosis. Moreover, as podocytes die, the remaining podocytes are unable to proliferate and replenish those lost, resulting in a decrease in podocyte number. This further reduces the barrier function of these cells and ultimately leads to kidney failure. The purpose of this grant is to define novel mechanisms underlying podocyte death. Our group has focused in molecules called cell cycle proteins, which reside in the nucleus of the cell. In this grant, we will test the hypothesis that newly discovered cell cycle proteins called cyclin I and cdk5 form a complex which functions to protect podocytes from death in disease. We also believe another partner called p21 adds to this protective function. We will explore possibilities using podocytes in a cell culture system, and also in mice that have been genetically altered to be born without cyclin I, cdk5 and p21. The overall goal is to delineate new paradigms in the regulation of podocyte survival and death, so that ultimately new strategies can be developed to prevent podocyte loss, enhance kidney survival, and reduce kidney disease.

描述（由申请人提供）：肾脏疾病在美国以流行病的速度增长。肾脏疾病的一个临床症状是尿中含有蛋白质（蛋白尿）。这通常是由于正常滤过屏障的泄漏，部分原因是由于足细胞的损伤。足细胞是一种特殊的细胞，其功能是限制蛋白尿。然而，在包括糖尿病在内的许多疾病中，足细胞被损伤到死亡的地步，称为细胞凋亡。此外，随着足细胞的死亡，剩余的足细胞无法增殖和补充失去的足细胞，导致足细胞数量减少。这进一步降低了这些细胞的屏障功能，最终导致肾衰竭。这项资助的目的是确定足细胞死亡的新机制。我们的研究小组专注于一种叫做细胞周期蛋白的分子，它存在于细胞核中。在这项资助中，我们将测试新发现的细胞周期蛋白cyclin I和cdk5形成一个复合物的假设，该复合物的功能是保护足细胞免于疾病死亡。我们还认为，另一种名为p21的伴侣也增强了这种保护功能。我们将探索在细胞培养系统中使用足细胞的可能性，以及在基因改变后出生时没有细胞周期蛋白1、cdk5和p21的小鼠中使用足细胞的可能性。总体目标是描述足细胞存活和死亡调控的新范式，从而最终制定新的策略来预防足细胞损失，提高肾脏存活率，减少肾脏疾病。