Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice
Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice
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DOI：
10.1016/j.bbrc.2007.12.041
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发表时间：
2008-02-15
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
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作者：
Goto, Hideo;Nishikawa, Takeshi;Araki, Eiichi
我们以前提出，高血糖诱导的线粒体活性氧的过度生产是糖尿病并发症的发展中的一个关键事件。在这项研究中，我们建立了一种新的转基因小鼠（eMnSOD-Tg），它特异性地表达MnSOD的内皮细胞，通过采用Tie 2启动子/增强子，并在体内研究线粒体ROS的产生对糖尿病视网膜病变的影响。使用免疫组织化学，MnSOD在内皮细胞中的过度表达被证实在eMnSOD-Tg小鼠。通过链脲佐菌素引入糖尿病，尿8-羟基脱氧鸟苷（线粒体氧化应激的标志物）水平以及视网膜中VEGF mRNA和蛋白质以及纤连蛋白mRNA的表达在野生型同窝仔中增加。然而，这些观察结果在eMnSOD-Tg小鼠中得到改善，尽管对照和eMnSOD-Tg小鼠显示出相当的高血糖水平。在本研究中，我们新开发的转基因小鼠系，它特异性地表达MnSOD在内皮细胞。此外，血管内皮细胞特异性超氧化物歧化酶的过度表达可以预防体内糖尿病视网膜病变。(c)2007年爱思唯尔公司All rights reserved.
We previously proposed that hyperglycemia-induced mitochondrial ROS overproduction is a key event in the development of diabetic complications. In this study, we established a novel transgenic mouse (eMnSOD-Tg), which specifically expressed MnSOD in endothelial cells, by employing a Tie2 promoter/enhancer, and investigated the impact of mitochondrial ROS production on diabetic retinopathy in vivo. Using immunohistochemistry, overexpression of MnSOD in endothelial cells was confirmed in eMnSOD-Tg mice. By introduction of diabetes by streptozotocin, levels of urinary 8-hydroxydeoxyguanosine, a marker of mitochondrial oxidative stress, and expression of VEGF mRNA and protein and fibronectin mRNA in retinas were increased in wild-type littermates. However, these observations were ameliorated in eMnSOD-Tg mice, although control and eMnSOD-Tg mice showed a comparable level of hyperglycemia. In the present study, we newly developed a line of transgenic mice, which specifically express MnSOD in endothelium. In addition, overexpression of mitochondrial-specific SOD in endothelium could prevent diabetic retinopathy in vivo. (c) 2007 Elsevier Inc. All rights reserved.