Podocyte Microenvironment in Diabetic Nephropathy

目前的建议对于糖尿病肾病研究PI的学术生涯发展至关重要。私家侦探认为，如果有机会实现他近期的职业目标；为了完善技能，获取知识，并促进学习进行这项研究所需的新方法，他将准备完成他的长期目标，即成为具有DN并发症专业知识的独立调查员。PI在糖尿病肾病领域做出了重大贡献，现在准备开始向独立的职业过渡。

The current proposal is critical for the development of an academic career for the PI in diabetes nephropathy research. The PI feels that if afforded the opportunity to achieve his immediate career goals; to refine the skills, to acquire knowledge and to facilitate learning new methodologies necessary to conduct this research study, he will be prepared to accomplish his long-term goal of developing into independent investigator with expertise in DN complications. The PI has made significant contributions to the field of diabetic kidney disease and is now poised to begin transitioning toward an independent career. Diabetes mellitus is the leading cause of end stage renal disease with markedly higher morbidity and mortality rates. Diabetes and diabetic nephropathy (DN) is a disorder of the immune system. Infiltration of the diseased kidneys by inflammatory cells such as monocytes/macrophages supports the role of inflammation as an etiological factor. In DN, alterations in the podocyte niche (microenvironment) are likely responsible for abnormal podocyte function leading to progressive albuminuria and progressive renal failure. Podocj^e function is intimately linked to its complex cytoskeletal structure. As a result of injury, cjrtoskeletal rearrangement ensues leading to foot process effacement We hj^othesize that macrophages contribute to direct podocyte injury and/or abnormal podocyte niche leading to DN and that adenosine A2A-agonist reverses this process and attenuates injury. Aim 1 tests the hypothesis that kidney macrophage recruitment directly contributes to diabetic renal injury. Aim 2 tests the hypothesis that macrophages directly mediate podocyte injury and/or create an abnormal podocyte niche leading to podocyte injury. Aim 3 tests the hypothesis that A2A-agonists ameliorate renal injury associated with DN by regulating macrophages/podocyte interaction and/or by directly affecting podocyte function.