The Role of Nephronectin in Glomerular Development and Function

肾连接素在肾小球发育和功能中的作用

基本信息

批准号：
10403972
负责人：
DENISE K MARCIANO
金额：
$ 36.45万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-20 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10403972
关键词：
3-Dimensional Adhesions Adhesives Adult Affect Area Behavior Binding Biology Biomechanics Blocking Antibodies Blood capillaries CSPG4 gene Cell Adhesion Cell Communication Cell physiology Cells Chronic Kidney Failure Complex Cultured Cells Data Defect Deposition Development Diabetic Nephropathy Dissection End stage renal failure Filtration Future Genes Genetic Histologic ITGA5 gene In Vitro Individual Integrin Binding Integrins Kidney Kidney Diseases Knowledge Laminin Ligands MAP Kinase Gene Maintenance Mechanics Mediating Membrane Proteins Modeling Molecular Mus Mutant Strains Mice Mutation Pathogenesis Pericytes Play Production Proteins Renal glomerular disease Research Resolution Role Sclerosis Signal Pathway Signal Transduction Stretching Structure Supporting Cell Testing Transforming Growth Factor beta Work base cell behavior glomerular basement membrane hypertensive in vivo insight mesangial cell migration nephrogenesis nephronectin new therapeutic target novel podocyte receptor reconstruction three-dimensional modeling tool

项目摘要

Project abstract: The glomerular basement membrane (GBM) forms a critical component of glomeruli, and is comprised of numerous proteins, many of whose individual functions are unknown. Much of the GBM is located between podocytes and endothelia, however, it also interacts directly with mesangial cells, a pericyte-like, contractile, support cell. Very little is known about the individual GBM proteins involved in this interaction and the role these interactions play in glomerular structure and function throughout development and in adulthood. In preliminary studies, we have identified a novel GBM-mesangial cell adhesion that contains the GBM protein nephronectin. We find that nephronectin is essential for development of the glomerular tuft, and also plays a role in maintenance of glomerular structure. We therefore propose to 1) determine the role of nephronectin in various stages of glomerulogenesis, 2) test its role in mediating stability of glomerular structure in mature kidneys, and 3) dissect the role of nephronectin-integrin signaling in cultured cells. Through these studies, we will greatly expand our understanding of GBM- mesangial cell interactions. Gaining molecular knowledge of these interactions and their function will be a critical step to understanding glomerular biology, and may contribute to directed therapies for glomerular disease.

项目摘要：肾小球基底膜（GBM）形成肾小球的关键成分，IS 由许多蛋白质组成，许多蛋白质的单个功能是未知的。大部分 GBM位于足细胞和内皮之间，但是，它也直接与肾小球细胞，一种细胞状的，收缩的，支撑细胞。对个人知之甚少 GBM蛋白参与这种相互作用以及这些相互作用在肾小球中的作用整个发展和成年期的结构和功能。在初步研究中，我们有鉴定出一种新型的GBM - 膜细胞粘附，其中包含GBM蛋白肾蛋白。我们发现肾上腺素对于开发肾小球簇是必不可少的，并且在维持肾小球结构。因此，我们建议1）确定在肾小球发生的各个阶段，肾扎蛋白，2）测试其在介导的稳定性中的作用成熟肾脏中的肾小球结构，3）剖析肾上腺素 - 整合蛋白信号的作用在培养的细胞中。通过这些研究，我们将大大扩展我们对GBM的理解膜细胞相互作用。获得这些相互作用及其功能的分子知识将是理解肾小球生物学的关键步骤，并可能有助于定向疗法用于肾小球疾病。