Is Diabetic Nephropathy the Result of a Podocyte Tauopathy?

糖尿病肾病是足细胞 Tau 蛋白病的结果吗？

• 批准号: MR/T002263/1
• 负责人: Richard Coward
• 金额: $ 80.42万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT002263%2F1
• 关键词: Diabetic; Nephropathy; Result; Podocyte; Tauopathy

Diabetic kidney disease (DKD) is the leading cause of kidney failure in the world and increasing at alarming rates due to the diabetes-inducing lifestyles we live. Currently the treatments for DKD are inadequate with many diabetic patients developing kidney failure needing dialysis or a kidney transplant. These patients are also more likely to suffer from cardiovascular problems such as heart attacks and strokes and to die early.It is also known that being diabetic and/or having kidney disease significantly increases the risk of developing dementia. We have evidence that this link may be due to accumulation of a protein called Tau in the cells of the brain and also in a key kidney cell called the podocyte. In this project we will investigate the importance of having too much "activated Tau" in the podocyte in diabetic and non-diabetic conditions. If we find this is an important factor that damages the kidney it will lead to the development of new types of drugs to prevent cellular Tau accumulation which will hopefully stop diabetic patients from developing kidney failure and the other associated severe problems.

糖尿病肾病(DKD)是世界上导致肾衰竭的主要原因，由于我们的生活方式导致糖尿病，它正以惊人的速度增长。目前，对DKD的治疗是不够的，许多糖尿病患者发展为肾衰竭，需要透析或肾移植。这些患者还更有可能患有心脏病发作和中风等心血管问题，并过早死亡。此外，众所周知，糖尿病和/或患有肾脏疾病显著增加了患痴呆症的风险。我们有证据表明，这种联系可能是由于一种名为Tau的蛋白质在脑细胞中积累，也是在关键的肾脏细胞中积累的足细胞。在这个项目中，我们将研究在糖尿病和非糖尿病条件下足细胞中有过多的“激活的Tau”的重要性。如果我们发现这是损害肾脏的一个重要因素，这将导致新型药物的开发，以防止细胞内Tau积聚，从而有望阻止糖尿病患者发展为肾衰竭和其他相关的严重问题。

项目成果

Extracellular RNA moves from the glomerulus to the renal tubule

• DOI: 10.1101/2021.06.15.448584
• 发表时间: 2021-06
• 期刊: bioRxiv
• 作者: R. Hunter;Sujai Kumar;R. Coward;A. Buck;J. Dear

Encyclopedia of Cell Biology

细胞生物学百科全书

• DOI: 10.1016/b978-0-12-394447-4.20047-3
• 发表时间: 2016
• 作者: Giese S

How to solve a clinical conundrum: Have you tried a trio exome analysis?

如何解决临床难题：您尝试过三外显子组分析吗？

• DOI: 10.1136/archdischild-2021-322910
• 发表时间: 2023
• 期刊: Archives of disease in childhood. Education and practice edition
• 作者: Beal F

Global proteomic analysis of insulin receptor interactors in glomerular podocytes.

• DOI: 10.12688/wellcomeopenres.16072.1
• 发表时间: 2020
• 期刊: Wellcome open research
• 作者: Hosawi SB;Humphries JD;Coward RJ;Knight D;Humphries MJ;Lennon R
• 通讯作者: Lennon R

The protective role of peroxisome proliferator-activated receptor gamma in lipotoxic podocytes.

• DOI: 10.1016/j.bbalip.2023.159329
• 发表时间: 2023-05
• 期刊: Biochimica et biophysica acta. Molecular and cell biology of lipids
• 作者: Almudena G Carrasco;Adriana Izquierdo-Lahuerta;Á. Valverde;L. Ni;Elena Flores-Salguero;R. Coward;G. Medina-Gómez