Role of Myosins in Podocyte Mechanical Force Generation

肌球蛋白在足细胞机械力产生中的作用

基本信息

批准号：
7193485
负责人：
JOEL M HENDERSON
金额：
$ 5.54万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2008-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7193485
关键词：
Actins Angiotensins Be++ element Beds Beryllium Blood capillaries Cell Line Cell physiology Clone Cells Complement Complementary DNA Contractile Proteins Cytochalasins Data Disease Progression Elements End stage renal failure Environment Face Fellowship Generations Goals Human Human Cell Line Hypertension Immunoblotting In Situ Individual Injury Intervention Isometric Contraction Isometric Exercise Kidney Diseases Lysophospholipids Measurement Measures Mechanics Messenger RNA Molecular Mus Myosin ATPase Names Pathologic Pathway interactions Phase Property Proteins RNA Interference Role Selection Criteria Site Structure System Techniques Testing Thinking Traction Work base capillary diacetylmonoxime glomerulosclerosis in vivo lysophosphatidic acid member novel strategies podocyte pressure protein function response serial analysis of gene expression

项目摘要

The objective of this project is to investigate the role of the podocyte as a structural element within the glomerulus. This function may be undermined in pathologic states associated with glomerular hypertension, resulting in podocyte injury and glomerulosclerosis. Thus, defining the role of the podocyte in maintaining glomerular structure in the face of mechanically unfavorable environments will help identify new approaches to delay kidney disease progression to end stage renal failure. The first phase of this project will characterize the potential of the podocyte to maintain a basal level of intracellular tension between attachment sites at the cellular processes, using cultured human podocytes grown on a well-characterized force measurement substrate. The next phase will investigate how the force-generating properties of podocytes change when the function of certain cytoskeletal elements, particularly myosin contractile proteins, is interfered with. Candidate myosins will be identified using publicly available serial analysis of gene expression (SAGE) data, and the effect of pharmacologic agents and mRNA interference upon the presence and mechanical function of these myosins will be assessed.

该项目的目的是研究足细胞作为结构元素的作用肾小球。该功能可能会在与肾小球高血压相关的病理状态下受到破坏，导致足细胞损伤和肾小球硬化。因此，定义足细胞在维护中的作用面对机械不利环境的肾小球结构将有助于识别新方法延迟肾脏疾病的进展到末期肾衰竭。该项目的第一阶段将表征足细胞维持基础细胞内张力水平的潜力使用培养的人足细胞在细胞过程中生长的培养的人足细胞的附着位点力测量基板。下一阶段将研究如何生成力的特性当某些细胞骨架元素的功能（尤其是肌球蛋白收缩）的功能时，足细胞会发生变化蛋白质会干扰。候选肌球蛋白将使用公开可用的序列分析来确定基因表达（SAGE）数据，以及药理学剂和mRNA干扰对这些肌动物的存在和机械功能将被评估。