Role of cadherin-11 in kidney fibrosis

我们最近发现钙粘蛋白-11(CDH11)在人类慢性肾脏疾病(CKD)和小鼠慢性肾脏疾病(CKD)模型的近曲小管中表达，并且在三种肾脏损伤模型中靶向CDH11可以减少纤维化和改善肾功能。因此，CDH11似乎是CKD的治疗靶点。我们假设CDH11的丢失通过保护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，并且这种保护提高了实验性CKD模型的死亡率。我们将通过建立小鼠近端小管CDH11(PT-CDH11)特异性缺失的模型来检验这一假设。缺乏PT-CDH11的小鼠的肾脏将接受单侧输尿管梗阻后的纤维化检查。

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.