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

通过调节肾小球前细胞中trpc介导的Ca2+信号，我们的目标是实现比阻断gpcr（如AT1R）更特异性的肾保护。使用高分辨率粒子分析，我们将表征肾切片模型（Cx40 GCaMP小鼠在表达Cx40的细胞中具有遗传编码的Ca2+传感器）肾小球前区域的一般细胞内Ca2+信号。特异性TRPC5/ c6介导的Ca2+信号将使用敲除小鼠和新的特异性抑制剂进行研究。基于代谢综合征（NZO）和亚急性慢性肾功能衰竭（UUO）小鼠模型中TRPC通道表达谱的改变，我们计划对这些小鼠模型中（修改的）Ca2+信号进行详细表征。

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.