Research in a experimental and clinical significance of uPAR as a new therapeutic target molecule for diabetic nephropathy

我们研究了uPAR作为一种新的糖尿病肾病治疗分子的作用。60%高脂饲料喂养12周后，uPAR基因敲除小鼠的体重、血清胰岛素水平、血清瘦素水平以及肾脏纤维连接蛋白和IV型胶原的表达水平均有所下降，而蛋白尿则无明显变化。在包括186名2型糖尿病患者的长期随访研究中(中位数：12年)，血清可溶性uPAR水平越高的亚组，肾功能障碍和心血管事件的累积发生率越高。因此，这些结果表明uPAR与糖尿病患者的肾功能障碍有关。

We investigated the role of uPAR as a new therapeutic molecule for diabetic nephropathy. The uPAR knockout mice fed 60% high-fat diet for 12 weeks showed the decrease of body weight, serum insulin levels, serum leptin levels, and the expression levels of fibronectin and type IV collagen in the kidney, whereas albuminuria was not different. In the long follow-up observational study(median : 12 years) including 186 patients with type 2 diabetes, the subgroup with higher levels of serum soluble uPAR showed the higher cumulative incidence of renal dysfunction and cardiovascular events. Thus, these results suggest that uPAR associates with renal dysfunction in diabetic patients.