Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice |
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Authors: | Goto Hideo Nishikawa Takeshi Sonoda Kazuhiro Kondo Tatsuya Kukidome Daisuke Fujisawa Kazuo Yamashiro Takeshi Motoshima Hiroyuki Matsumura Takeshi Tsuruzoe Kaku Araki Eiichi |
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Affiliation: | Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan |
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Abstract: | 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. |
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Keywords: | Diabetes Diabetic complications Reactive oxygen species Manganese superoxide dismutase Endothelium |
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