Adiponectin and Podocytes

脂联素和足细胞

基本信息

批准号：
8394597
负责人：
Kumar Sharma
金额：
--
依托单位：
VA SAN DIEGO HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-10-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8394597
关键词：
Adherence Adipocytes Affect African American Aging Albuminuria American Binding Cells Coupled Cytosol Data Development Diabetes Mellitus Diabetic mouse Dominant-Negative Mutation Energy Intake Enzymes Epidemic Foot Process Herpes zoster disease High Prevalence Hormones Hypertension Incidence Kidney Kidney Diseases Knockout Mice Mediating Membrane Proteins Metformin Morbidity - disease rate Mus Obesity Obesity associated kidney disease Pathway interactions Patients Pharmaceutical Preparations Phosphorylation Phosphotransferases Play Population Predisposition Proteins Proteomics Receptor Signaling Regulation Role Signal Pathway Small Interfering RNA Staging Structure Testing Translations United States Department of Veterans Affairs Veterans Viral Work abstracting adiponectin base glomerular basement membrane high risk in vivo in vivo Model podocyte protective effect public health relevance receptor response young adult

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract We have recently identified that circulating adiponectin levels negatively correlate with albuminuria in obese African Americans. As the incidence of kidney disease is extremely high in African Americans and the mechanisms of obesity related kidney disease are unclear, our proposal will focus on this highly significant topic to the VA population. The podocyte appears to be the main target cell by which adiponectin confers its protective action. In the present proposal we will identify the adiponectin receptors and signaling pathways by which adiponectin confers benefits to the podocytes and examine the key role of adiponectin in regulating an enzyme called AMPK. We have identified that AMPK is decreased in adiponectin deficient mice and in podocytes from diabetic mice. Administration of adiponectin restores AMPK activity and appears to protect podocytes from albuminuria. A key target of AMPK on podocytes appears to be the protein ZO-1 which has been shown to be intimately involved in the adherence of the podocyte foot processes to the glomerular basement membrane. The proposal aims to identify the key signaling receptors for adiponectin on podocytes, identify the role of AMPK and identify the proteins regulated by adiponectin and AMPK in mice. The studies will be of direct benefit to the VA population as there are existing drugs that regulate adiponectin levels and its signaling pathways, and thus may potentially offer new therapies for this population that is at high risk for kidney disease.

描述（由申请人提供）：项目摘要/摘要我们最近发现，在肥胖的非洲裔美国人中，循环脂联素水平与白蛋白尿呈负相关。由于非裔美国人的肾脏疾病发病率极高，且肥胖相关肾脏疾病的机制尚不清楚，因此我们的提案将重点关注这一对退伍军人事务部人群非常重要的主题。足细胞似乎是脂联素发挥保护作用的主要靶细胞。在本提案中，我们将确定脂联素受体和信号通路，脂联素通过这些受体和信号通路为足细胞带来益处，并研究脂联素在调节 AMPK 酶中的关键作用。我们已经发现，脂联素缺乏的小鼠和糖尿病小鼠的足细胞中 AMPK 降低。施用脂联素可以恢复 AMPK 活性，并且似乎可以保护足细胞免受白蛋白尿的影响。 AMPK 在足细胞上的一个关键靶标似乎是蛋白质 ZO-1，该蛋白已被证明与足细胞足突与肾小球基底膜的粘附密切相关。该提案旨在鉴定小鼠足细胞上脂联素的关键信号受体、AMPK的作用以及鉴定脂联素和AMPK调节的蛋白质。这些研究将直接惠及 VA 人群，因为现有药物可以调节脂联素水平及其信号通路，因此可能为这一肾病高危人群提供新的治疗方法。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Oxidative stress, inflammation and cardiovascular disease in chronic renal failure.

慢性肾衰竭中的氧化应激、炎症和心血管疾病。

DOI：
发表时间：
2008-03-01
期刊：
Journal of nephrology
影响因子：
3.4
作者：
S. Cottone;M. C. Lorito;R. Riccobene;E. Nardi;G. Mulè';S. Buscemi;C. Geraci;M. Guarneri;R. Arsena
通讯作者：
R. Arsena

Obesity and kidney disease: differential effects of obesity on adipose tissue and kidney inflammation and fibrosis.

肥胖和肾脏疾病：肥胖对脂肪组织以及肾脏炎症和纤维化的不同影响。