Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice
Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice
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DOI：
10.1152/ajprenal.00065.2010
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Tomino, Yasuhiko
中科院分区：
文献类型：
--
作者：
Moon, Ju-Young;Tanimoto, Mitsuo;Tomino, Yasuhiko
Moon JY，Tanimoto M，Gohda T，Hagiwara S，Yamazaki T，大原I，Murakoshi M，Aoki T，石川Y，Lee SH，Jeong KH，Lee TW，Ihm CG，Lim SJ，Tomino Y.血管紧张素-（1-7）对KK-A（y）/Ta小鼠2型糖尿病肾病血管紧张素II介导的NAD（P）H氧化酶活化的减弱作用美国肾脏生理学杂志300：F1271-F1282，2011年。首次发表于2011年3月2日; doi：10.1152/ajprenal.00065.2010.- ANG-（1-7）与血管舒张和一氧化氮合酶刺激有关。然而，ANG-（1-7）在2型糖尿病中的作用尚不清楚。在这项研究中，我们检验了ANG-（1-7）减弱ANG II诱导的活性氧应激（ROS）介导的KK-A（y）/Ta小鼠2型糖尿病肾病损伤的假设。将KK-A（y）/Ta小鼠分为4组：1）对照组; 2）ANG II输注组; 3）ANG II + ANG-（1-7）共输注组; 4）ANG II + ANG-（1-7）+ D-Ala（7）-ANG-（1-7）（A779）共输注组。此外，培养原代系膜细胞，然后用25 mM葡萄糖刺激，加入或不加入ANG II、ANG-（1-7）和A779。ANG II + ANG-（1-7）联合输注组的尿白蛋白/肌酐比值增加低于ANG II组。ANG-（1-7）减弱ANG II介导的糖尿病肾小球和系膜细胞中NAD（P）H氧化酶活化和ROS产生。ANG-（1-7）也可减弱ANG II诱导的系膜细胞NF-κ B和MAPK信号通路的激活。这些发现与改善系膜扩张和纤维连接蛋白和转化生长因子β 1的产生有关，提示ANG-（1-7）可能减弱ANG II刺激的ROS介导的2型糖尿病肾病损伤。ACE 2-ANG-（1-7）-Mas受体轴可作为治疗2型糖尿病肾病的新靶点。
Moon JY, Tanimoto M, Gohda T, Hagiwara S, Yamazaki T, Ohara I, Murakoshi M, Aoki T, Ishikawa Y, Lee SH, Jeong KH, Lee TW, Ihm CG, Lim SJ, Tomino Y. Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P) H oxidase activation in type 2 diabetic nephropathy of KK-A(y)/Ta mice. Am J Physiol Renal Physiol 300: F1271-F1282, 2011. First published March 2, 2011; doi:10.1152/ajprenal.00065.2010.-ANG-(1-7) is associated with vasodilation and nitric oxide synthase stimulation. However, the role of ANG-(1-7) in type 2 diabetes mellitus is unknown. In this study, we examined the hypothesis that ANG-(1-7) attenuates ANG II-induced reactive oxygen species stress (ROS)-mediated injury in type 2 diabetic nephropathy of KK-A(y)/Ta mice. KK-A(y)/Ta mice were divided into four groups: 1) a control group; 2) ANG II infusion group; 3) ANG II + ANG-(1-7) coinfusion group; and 4) ANG II + ANG-(1-7) + D-Ala(7)-ANG-(1-7) (A779) coinfusion group. In addition, primary mesangial cells were cultured and then stimulated with 25 mM glucose with or without ANG II, ANG-(1-7), and A779. The ANG II + ANG-(1-7) coinfusion group showed a lower urinary albumin/creatinine ratio increase than the ANG II group. ANG-(1-7) attenuated ANG II-mediated NAD(P) H oxidase activation and ROS production in diabetic glomeruli and mesangial cells. ANG II-induced NF-kappa B and MAPK signaling activation was also attenuated by ANG-(1-7) in the mesangial cells. These findings were related to improved mesangial expansion and to fibronectin and transforming growth factor-beta 1 production in response to ANG II and suggest that ANG-(1-7) may attenuate ANG II-stimulated ROS-mediated injury in type 2 diabetic nephropathy. The ACE2-ANG-(1-7)-Mas receptor axis should be investigated as a novel target for treatment of type 2 diabetic nephropathy.