EDA2R is a member of the large family of tumor necrosis factor receptor (TNFR). Previous studies suggested that EDA2R expression might be increased in the kidneys of diabetic mice. However, its mRNA and protein expression in kidneys were not analyzed; moreover, its role in the development of diabetic kidney disease was not explored. Here we analyzed the mRNA and protein expressions of EDA2R in diabetic kidneys and examined its role in the podocyte injury in high glucose milieu. By analysis with real-time PCR, Western blotting, we found that both the mRNA and protein levels of EDA2R were increased in the kidneys of diabetic mice. Immunohistochemical studies revealed that EDA2R expression was enhanced in both glomerular and tubular cells of diabetic mice and humans. In vitro studies, high glucose increased EDA2R expression in cultured human podocytes. Overexpression of EDA2R in podocytes promoted podocyte apoptosis and decreased nephrin expression. Moreover, ED2AR increased ROS generation in podocytes, while inhibiting ROS generation attenuates EDA2R-mediated podocyte injury. In addition, EDA2R silencing partially suppressed high glucose-induced ROS generation, apoptosis, and nephrin decrease. Our study demonstrated that high glucose increases EDA2R expression in kidney cells and that EDA2R induces podocyte apoptosis and dedifferentiation in high glucose milieu partially through enhanced ROS generation.

中文翻译：

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EDA2R介导高糖环境中的足细胞损伤。

EDA2R是肿瘤坏死因子受体（TNFR）大家族的成员。先前的研究表明，EDA2R表达可能在糖尿病小鼠的肾脏中增加。然而，没有分析其在肾脏中的mRNA和蛋白质表达；此外，尚未探讨其在糖尿病肾病发展中的作用。在这里，我们分析了糖尿病肾脏中EDA2R的mRNA和蛋白质表达，并检查了其在高糖环境中足细胞损伤中的作用。通过实时PCR，蛋白质印迹分析，我们发现糖尿病小鼠肾脏中EDA2R的mRNA和蛋白水平均升高。免疫组织化学研究表明，在糖尿病小鼠和人类的肾小球和肾小管细胞中，EDA2R表达均得到增强。体外研究 高葡萄糖可提高培养的人足细胞中EDA2R的表达。EDA2R在足细胞中的过表达促进足细胞凋亡并降低肾素的表达。此外，ED2AR增加了足细胞中ROS的生成，而抑制ROS生成则减弱了EDA2R介导的足细胞损伤。此外，EDA2R沉默部分抑制了高糖诱导的ROS的产生，凋亡和肾素的降低。我们的研究表明，高糖可增加肾细胞中EDA2R的表达，而EDA2R可通过增强ROS的产生部分地诱导高糖环境中足细胞凋亡和去分化。同时抑制ROS的产生可减弱EDA2R介导的足细胞损伤。此外，EDA2R沉默部分抑制了高葡萄糖诱导的ROS生成，凋亡和肾素的降低。我们的研究表明，高糖可增加肾细胞中EDA2R的表达，而EDA2R可通过增强ROS的产生部分地诱导高糖环境中足细胞凋亡和去分化。同时抑制ROS的产生可减弱EDA2R介导的足细胞损伤。此外，EDA2R沉默部分抑制了高葡萄糖诱导的ROS生成，凋亡和肾素的降低。我们的研究表明，高糖可增加肾细胞中EDA2R的表达，而EDA2R可通过增强ROS的产生部分地诱导高糖环境中足细胞凋亡和去分化。