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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 法舒地尔抑制 Rho 激酶 (ROCK) 活性可改善糖尿病进展 肾病（DN）。但法舒地尔没有选择性，不能区分 ROCK-1 与 ROCK-2（ROCK 的两种不同异构体）在 DN 中的致病作用。因此在 目前的研究，我们将使用遗传方法。我们在 FVB 上生成了 ROCK1-/- 小鼠 背景。这些小鼠表型正常。 具体目的：评估 ROCK1 对线粒体碎片的作用。 我们观察到 ROCK1-/- 糖尿病小鼠的 与野生型糖尿病小鼠相比，线粒体断裂。因此，我们是 计划评估 ROCK1 对肾小球线粒体碎片的作用 具有 2D 和 3D EM 的足细胞。 为此，不对糖尿病小鼠和糖尿病小鼠进行灌注，并对它们的肾脏进行固定和 准备染色、塑料包埋和切片。 根据之前的研究，我们计划从序列中重建线粒体结构 代表性区域的切片以确认线粒体碎片 来自糖尿病小鼠的足细胞。