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

足细胞胸腺素-β4 在健康和患病肾小球中的作用

• 批准号: MR/J003638/1
• 负责人: David Long
• 金额: $ 61.61万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ003638%2F1
• 关键词: role; podocyte; thymosin; beta4; healthy

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.

长期严重的严重肾脏疾病只能通过透析或移植来治疗，在过去的十年中，需要这种类型的支持的人数增加了一倍。现在，它影响了每百万人口100人，并且正在增加。肾脏疾病的一个关键特征是对过滤单元的中断，该单元是由几种不同细胞类型产生的高度复杂的结构。这些细胞之一是足细胞，具有高度分支的形状，这对于其功能至关重要。这种形状的破坏是许多童年和成人肾脏疾病的特征，例如最小的变化疾病和糖尿病肾脏疾病，会导致尿液中蛋白质的损失，如果持续到终阶段肾脏疾病。因此，首先了解足细胞形状如何发展，可以提供受伤后恢复其必要的知识，从而大大改善许多肾脏疾病的治疗。在这个项目中，我将研究一个称为胸腺素β4的分子的作用，该分子在足细胞中高度表达并参与维持细胞形状。开发其他器官（例如心脏）的关键，目前正在临床试验中进行调查，以此作为对伤口愈合和心肌梗塞等疾病的潜在治疗方法。在这项新的研究者奖中，我将研究胸腺素β4在肾脏的发育和成熟过滤障碍以及肾脏疾病实验模型中所做的工作。如果对胸腺素β4的调节减慢了肾脏疾病的进展，那么对于这些​​患者来说，这可能是新的令人兴奋的治疗途径。

项目成果

Diabetic Nephropathy - Methods and Protocols

糖尿病肾病 - 方法和方案

• DOI: 10.1007/978-1-4939-9841-8_8
• 发表时间: 2020
• 作者: Jafree D

Albuminuria is associated with too few glomeruli and too much testosterone.

• DOI: 10.1038/ki.2013.45
• 发表时间: 2013-06
• 期刊: Kidney international
• 影响因子: 19.6

Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning.

• DOI: 10.1016/j.kint.2016.07.011
• 发表时间: 2016-12
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Brzoska, Hortensja L.;d'Esposito, Angela M.;Kolatsi-Joannou, Maria;Patel, Vishal;Igarashi, Peter;Lei, Yunping;Finnell, Richard H.;Lythgoe, Mark F.;Woolf, Adrian S.;Papakrivopoulou, Eugenia;Long, David A.
• 通讯作者: Long, David A.