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

点击翻译按钮获取中文摘要

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.