The role of podocyte thymosin-beta4 in the healthy and diseased glomerulus

长期严重的肾脏疾病只能通过透析或移植来治疗，在英国，需要这种支持的人数在过去十年中翻了一番。现在每百万人中就有100人受到影响，而且还在上升。肾脏疾病的一个关键特征是过滤单元的破坏，过滤单元是由几种不同的细胞类型产生的高度复杂的结构。其中一种细胞，足细胞，具有高度分支的形状，这对其功能至关重要。这种形状的破坏是许多儿童和成人肾脏疾病的特征，如微小变化疾病和糖尿病肾病，导致尿中蛋白质的损失，如果持续到终末期肾病。因此，首先了解足细胞形状是如何形成的，可以提供损伤后恢复足细胞所需的知识，从而大大改善许多肾脏疾病的治疗。在这个项目中，我将研究一种名为胸腺素- β 4的分子的作用，这种分子在足细胞中高度表达，并参与维持细胞形状；对心脏等其他器官的发育至关重要，目前正在临床试验中作为伤口愈合和心肌梗死等疾病的潜在治疗方法进行研究。在这个新研究者奖中，我将研究胸腺素- β 4在肾脏的发育和成熟的过滤屏障以及肾脏疾病的实验模型中的作用。如果调节胸腺素- β 4可以减缓肾脏疾病的进展，它可能是未来治疗这些患者的一种新的令人兴奋的治疗途径。

Long term severe kidney disease can only be treated by dialysis or transplantation, and the number of people needing this type of support has doubled in frequency over the last ten years in the UK. It now affects 100 people per million population and is rising. One key feature of kidney disease is disruption to the filtration unit which is a highly complex structure created from several different cell types. One of these cells, the podocyte, has a highly branched shape which is essential for its function. Disruption to this shape, a feature of many childhood and adult kidney diseases such as minimal change disease and diabetic kidney disease, leads to loss of protein in the urine and if persistent to end stage kidney disease. Therefore, understanding how podocyte shape develops in the first place, could provide the knowledge necessary to restore it after injury and thus greatly improve treatment of many kidney diseases. In this project, I will study the role of a molecule called thymosin-beta4 which is highly expressed in podocytes and involved in maintaining cell shape; key to the development of other organs such as the heart and currently being investigated in clinical trials as a potential treatment for diseases such as wound healing and myocardial infarction. In this New Investigator award, I will look at what thymosin-beta4 does in the developing and mature filtration barrier of the kidney and in an experimental model of kidney disease. If modulation of thymosin-beta4 slows the progression of kidney disease, it could be a new exciting therapeutic avenue for these patients in the future.