Role of cadherin-11 in kidney fibrosis

我们最近发现cadherin-11 （CDH11）在慢性肾脏疾病（CKD）人和小鼠模型的近端小管中表达，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的治疗靶点。我们假设CDH11的缺失通过保持近端小管的健康和功能来阻止近端小管上皮细胞的凋亡和CKD的进展，并且这种保存提高了CKD实验模型的死亡率。我们将通过建立CDH11近端小管特异性缺失（PT-CDH11）的小鼠模型来验证这一假设。缺乏PT-CDH11小鼠的肾脏将在单侧输尿管梗阻后进行纤维化检查。

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.