Targeting renoprotection downstream of the angiotensin II type 1 receptor (A05)

靶向血管紧张素 II 1 型受体下游的肾脏保护 (A05)

• 批准号: 418369855
• 金额: --
• 依托单位: Institut für Vegetative Physiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418369855?language=en
• 关键词: Targeting; renoprotection; downstream; angiotensin; II

By modulating TRPC-mediated Ca2+ signaling in pre-glomerular cells, we aim to achieve renoprotection that is more specific than blockade of GPCRs such as AT1R. Using high-resolution particle analysis, we will characterize the general intracellular Ca2+ signals in the pre-glomerular region of a kidney slice model (Cx40 GCaMP mouse with a genetically encoded Ca2+ sensor in Cx40-expressing cells). Specific TRPC5/C6-mediated Ca2+ signals will be studied using knock-out mice and novel specific inhibitors. Based on an altered expression profile of TRPC channels in mouse models of metabolic syndrome (NZO) and subacute chronic renal failure (UUO), we plan a detailed characterization of the (modified) Ca2+ signals in these mouse models.

通过调节TRPC介导的前肾小球细胞中的Ca 2+信号传导，我们的目标是实现比阻断GPCR（如AT 1 R）更特异的肾脏保护。使用高分辨率颗粒分析，我们将表征肾切片模型（在Cx40表达细胞中具有遗传编码的Ca 2+传感器的Cx40 GCaMP小鼠）的肾小球前区中的一般细胞内Ca 2+信号。将使用基因敲除小鼠和新型特异性抑制剂研究特异性TRPC 5/C6介导的Ca 2+信号。基于TRPC通道在代谢综合征（NZO）和亚急性慢性肾功能衰竭（UUO）小鼠模型中的表达谱改变，我们计划在这些小鼠模型中详细描述（经修饰的）Ca 2+信号。