The Role of Cdk5 in Podocyte Biology

Cdk5 在足细胞生物学中的作用

• 批准号: 198523828
• 负责人: Professor Dr. Paul-Thomas Brinkkötter
• 金额: --
• 依托单位: Klinik II für Innere Medizin: Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198523828?language=en
• 关键词: Role; Cdk5; Podocyte; Biology

Glomerular diseases are a leading cause of chronic and end stage kidney failure. The terminally differentiated and highly specialized glomerular epithelial cell, the podocyte, is a critical component of the glomerular filtration barrier, and required for normal glomerular integrity. Loss of podocytes due to apoptosis and detachment of the cells from the glomerular basement membrane (GBM) contributes to the development of kidney diseases resulting in proteinuria and glomerulosclerosis. Thus, understanding regulatory mechanisms ascertaining podocyte function and survival is of major importance. We have shown that both, p35 and cyclin I mediated cyclin dependent kinase (Cdk) 5 activity is crucial for podocyte survival following acquired injury. Cdk5 is an atypical Cdk that is not involved in cell cycle regulation but rather controls cellular differentiation. In this project we will (i) investigate how Cdk5 regulates glomerular biology, (ii) identify components of the Cdk5 pathway and characterize regulatory principles of the signalling network involved and (iii) unravel the role of atypical cyclin-dependent kinases in the pathogenesis of renal diseases. We expect that our results will lead to a better understanding of a large group of glomerular disorders that is characterized by the development of proteinuria and kidney failure.

肾小球疾病是慢性和终末期肾衰竭的主要原因。终末分化和高度特化的肾小球上皮细胞足细胞是肾小球滤过屏障的重要组成部分，是正常肾小球完整性所必需的。肾小球基底膜（GBM）细胞的凋亡和脱离导致足细胞的损失，有助于肾脏疾病的发展，导致蛋白尿和肾小球硬化。因此，了解足细胞功能和存活的调节机制是非常重要的。我们已经证明，p35和细胞周期蛋白I介导的细胞周期蛋白依赖性激酶（Cdk） 5活性对获得性损伤后足细胞存活至关重要。Cdk5是一种非典型Cdk，它不参与细胞周期调节，而是控制细胞分化。在这个项目中，我们将(i)研究Cdk5如何调节肾小球生物学，（ii）识别Cdk5途径的成分并表征所涉及的信号网络的调节原理，以及（iii）揭示非典型细胞周期蛋白依赖性激酶在肾脏疾病发病机制中的作用。我们期望我们的结果将导致更好地理解以蛋白尿和肾衰竭发展为特征的一大组肾小球疾病。