Identifying New Molecular Pathways and Therapeutic Targets in Diabetic Kidney Disease

糖尿病肾病（DKD）是世界上肾衰竭的主要原因，并且由于我们的生活方式导致糖尿病的生活方式而以惊人的速度增加。目前对DKD的治疗不足，许多患者出现肾衰竭，需要透析或肾移植。如果发生这种情况，这些患者更有可能患上心脏病和中风等心血管疾病，更有可能过早死亡。我们实验室的研究表明，在肾脏的过滤单元中，有一种叫做足细胞的细胞在DKD的发展中很重要，糖尿病的主要激素胰岛素能够向这个细胞发出有益的信号。当足细胞-胰岛素信号丢失时，它对肾脏功能和肾脏疾病是有害的。我们已经开发了一种药物筛选试验，以确定使足细胞对胰岛素更敏感的新疗法，这个项目已经确定了一个我们想要跟进的细胞靶点。我们打算在DKD小鼠模型和人足细胞培养皿中研究该靶点，以阐明它是否可能在未来治疗糖尿病肾病患者。

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 and many patients develop kidney failure needing dialysis or a kidney transplant. If this happens these patients are more likely to suffer from cardiovascular problems such as heart attacks and stroke and are much more likely to die prematurely.Work by our laboratory has shown that a cell in the filtering unit of the kidney called the podocyte is important in the development of DKD and that the major hormone in diabetes, insulin, is able to beneficially signal to this cell. When podocyte-insulin signalling is lost it is detrimental to kidney function and kidney disease develops. We have developed a drug screening assay to identify new therapies that make the podocyte more insulin-sensitive and this project has identified a cell target we would like to follow up. We intend studying this target in mouse models of DKD and human podocyte cells in dishes to clarify if it might be a good treatment for patients with diabetic kidney disease in the future.