Role of cadherin-11 in kidney fibrosis

cadherin-11在肾纤维化中的作用

基本信息

批准号：
10688739
负责人：
WILLIAM D MERRYMAN
金额：
$ 10万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10688739
关键词：
Address Affect American Angiotensin II Apoptosis Aristolochic Acids Biological Markers Blood Glucose CRISPR/Cas technology Cadherins Cell Adhesion Molecules Cell-Cell Adhesion Cells Chronic Kidney Failure Cicatrix Contracts Data Diet Disease Disease Progression Epithelial Cells Event Exons Experimental Models Fibroblasts Fibrosis Functional disorder Genetic Goals Health Healthcare Systems Hematopoietic Human Hypertension Inflammation Inflammatory Injury Injury to Kidney Kidney Kidney Diseases Knockout Mice Lead LoxP-flanked allele Mediator of activation protein Medicare Mesenchymal Modeling Molecular Monoclonal Antibodies Mus Myocardial Infarction Myofibroblast Natural regeneration Pharmaceutical Preparations Pharmacology Process Pump Regulation Renal function Rheumatoid Arthritis Role Signal Transduction Tamoxifen Testing Therapeutic Tissues Tubular formation Ureteral obstruction aortic valve disorder blood pressure reduction cadherin-11 cell injury cost epithelial injury healing heart function implantation improved injured inorganic phosphate kidney fibrosis macrophage monocyte mortality mouse model neutrophil novel therapeutic intervention preservation prevent recruit therapeutic target

项目摘要

We have recently found that cadherin-11 (CDH11) is expressed in proximal tubules of human cases and mouse models of chronic kidney disease (CKD) and that targeting CDH11 in three models of kidney injury reduces fibrosis and improves renal function. Hence, CDH11 appears to be a therapeutic target for CKD. We hypothesize that loss of CDH11 prevents apoptosis of proximal tubule epithelial cells and the progression of CKD by preserving proximal tubule health and function, and that this preservation improves mortality in experimental models of CKD. We will test this hypothesis by developing a mouse model of proximal tubule specific deletion of CDH11 (PT-CDH11). Kidneys from mice lacking PT-CDH11 will be examined for fibrosis following unilateral ureter obstruction.

我们最近发现，Cadherin-11（CDH11）在人类病例的近端小管和慢性肾脏疾病（CKD）的小鼠模型中表达，并且在三种肾损伤模型中靶向CDH11可减少纤维化并改善肾功能。因此，CDH11似乎是CKD的治疗靶标。我们假设CDH11的丧失可以防止近端小管上皮细胞的凋亡以及通过保留近端小管健康和功能的CKD的进展，并且这种保存在CKD实验模型中提高了死亡率。我们将通过开发CDH11（PT-CDH11）的近端小管特异性缺失的小鼠模型来检验这一假设。单侧输尿管阻塞后，将检查缺乏PT-CDH11的小鼠的肾脏是否有纤维化。