Role of Bim and apoptosis in the development of polycystic kidney disease (PKD) (C03)

Bim 和细胞凋亡在多囊肾病 (PKD) 发展中的作用 (C03)

• 批准号: 267202053
• 金额: --
• 依托单位: Institut für Molekulare Medizin und Zellforschung
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/267202053?language=en
• 关键词: Role; Bim; apoptosis; development; polycystic

Mice deficient of the survival factor Bcl-2 develop polycystic kidney disease (PKD) that is mediated via the pro-apoptotic BH3-only protein Bim, but how apoptosis contributes to the disease is unknown. Moreover, it has been unclear if other BH3-only proteins such as Puma participate in the process and if apoptosis is also crucial for the emergence of the slowly progressing, late-onset autosomal dominant polycystic kidney disease (ADPKD) in humans caused by mutations in the polycystin-1 gene Pkd1. In this proposal we will use mice lacking Bci-2 or Pkd1 (kidney specific or induced) and isolated kidney cells of these mice to determine if and how Bim and/or Puma contribute to cystogenesis and PKD.

缺乏存活因子Bcl-2的小鼠发展为多囊肾病（PKD），其通过促凋亡BH 3-only蛋白Bim介导，但凋亡如何促成该疾病尚不清楚。此外，目前还不清楚其他仅BH 3蛋白（如Puma）是否参与该过程，以及细胞凋亡是否也是由多囊蛋白-1基因Pkd 1突变引起的人类缓慢进展的晚发型常染色体显性多囊肾病（ADPKD）的关键。在本提案中，我们将使用缺乏Bci-2或Pkd 1的小鼠（肾特异性或诱导性）和这些小鼠的分离的肾细胞来确定Bim和/或Puma是否以及如何促进囊肿形成和PKD。