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.

长期严重肾脏疾病只能通过透析或移植来治疗，在过去十年中，英国需要此类支持的人数增加了一倍。现在每百万人口中有 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细胞类型创建的高度复杂的结构。其中一种细胞，即足细胞，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（例如微小病变肾病和糖尿病肾病）的一个特征，会导致尿液中蛋白质的流失，如果持续存在，则会导致终末期肾病。因此，首先了解足细胞形状如何发育，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-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；它是心脏等其他器官发育的关键，目前正在临床试验中作为伤口愈合和心肌梗塞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-β4 在肾脏滤过屏障的发育和成熟以及肾脏疾病实验模型中的作用。如果胸腺素-β4 的调节能够减缓肾脏疾病的进展，那么未来对于这些患者来说这可能是一个令人兴奋的新治疗途径。

项目成果

Targeted glomerular angiopoietin-1 therapy for early diabetic kidney disease.

靶向肾小球血管生成素-1 治疗早期糖尿病肾病。

• DOI: http://dx.10.1681/asn.2012121218
• 发表时间: 2014
• 期刊: JASN
• 作者: Dessapt

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

平面细胞极性基因 Celsr1 和 Vangl2 对于肾脏生长、分化和轴尾模式至关重要。

• DOI: http://dx.10.1016/j.kint.2016.07.011
• 发表时间: 2016
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Brzóska HL

Planar cell polarity in organ formation.

器官形成中的平面细胞极性。

• DOI: 10.1016/j.ceb.2018.06.011
• 发表时间: 2018-12-01
• 期刊: Current opinion in cell biology
• 影响因子: 7.5
• 作者: D. Henderson;D. Long;C. Dean
• 通讯作者: C. Dean

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

蛋白尿与肾小球过少和睾酮过多有关。

• DOI: http://dx.10.1038/ki.2013.45
• 发表时间: 2013
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Long DA

Angiogenesis and autosomal dominant polycystic kidney disease.

血管生成和常染色体显性多囊肾病。

• DOI: http://dx.10.1007/s00467-012-2305-7
• 发表时间: 2013
• 期刊: Pediatric nephrology (Berlin, Germany)
• 作者: Huang JL