ROCK1 IN DIABETIC NEPHROPATHY

糖尿病肾病中的 ROCK1

• 批准号: 8361113
• 负责人: FARHAD R DANESH
• 金额: $ 1.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361113
• 关键词: Diabetic Nephropathy; Diabetic mouse; Electron Microscopy; Funding; Genetic; Grant; Isomerism; Kidney; Mitochondria; Mus; National Center for Research Resources; Plastic Embedding; Principal Investigator; ROCK1 gene; Research; Research Infrastructure; Resources; Rho-associated kinase; Role; Source; Staining method; Stains; Structure; United States National Institutes of Health; base; cost; diabetic; fasudil; macromolecule; podocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Inhibition of Rho kinase (ROCK) activity by fasudil ameliorates progression of diabetic nephropathy (DN). However, fasudil is not selective, and can not distinguish the pathogenic roles of ROCK-1 vs. ROCK-2, two different isomers of ROCK, in DN. Therefore in the current study, we will use a genetic approach. We generated ROCK1-/- mice on FVB background. These mice are phenotypically normal. Specific Aim: To evaluate the role of ROCK1 on mitochondrial fragmentation. We observed that ROCK1-/- diabetic mice demonstrated a significant reduction in mitochondrial fragmentation compared to wild type diabetic mice. Therefore, we are planning to evaluate the role of ROCK1 on mitochondrial fragmentation in glomerular podocytes with 2D and 3D EM. To this end, none diabetic and diabetic mice will be perfused, and their kidneys fixed and prepared for stained, plastic embedding and sectioning. Based on a previous study, we plan to reconstruct mitochondrial structure from serial sections of a representative region to confirm the mitochondrial fragmentation in podocytes from diabetic mice.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 通过Fasudil抑制Rho激酶（岩石）活性可改善糖尿病的进展 肾病（DN）。但是，Fasudil不是选择性的，也无法区分 岩石1与岩石2的致病作用，岩石的两个不同的异构体，在DN中。因此 当前的研究，我们将使用一种遗传方法。我们在FVB上产生了岩石1 - / - 小鼠 背景。这些小鼠在表型上是正常的。 具体目的：评估Rock1在线粒体碎片化中的作用。 我们观察到岩石1 - / - 糖尿病小鼠显示出显着降低 与野生型糖尿病小鼠相比，线粒体碎片化。因此，我们是 计划评估Rock1在肾小球中线粒体碎片化的作用 具有2D和3D EM的足细胞。 为此，没有任何糖尿病和糖尿病小鼠会被灌注，它们的肾脏固定了， 准备用于染色的塑料嵌入和切片。 基于先前的研究，我们计划通过串行重建线粒体结构 代表区域的部分确认线粒体碎片 来自糖尿病小鼠的足细胞。