Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice.
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.
Goto
Hideo
H
Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Nishikawa
Takeshi
T
Sonoda
Kazuhiro
K
Kondo
Tatsuya
T
Kukidome
Daisuke
D
Fujisawa
Kazuo
K
Yamashiro
Takeshi
T
Motoshima
Hiroyuki
H
Matsumura
Takeshi
T
Tsuruzoe
Kaku
K
Araki
Eiichi
E
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D013482:Superoxide Dismutase