Modulation of Nrf2 expression alters high glucose-induced oxidative stress and antioxidant gene expression in mouse mesangial cells
Modulation of Nrf2 expression alters high glucose-induced oxidative stress and antioxidant gene expression in mouse mesangial cells
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DOI：
10.1016/j.cellsig.2011.05.016
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发表时间：
2011-10-01
影响因子：
4.8
通讯作者：
Duan, Huijun
中科院分区：
文献类型：
--
作者：
Li, Hang;Wang, Fuxu;Duan, Huijun
活性氧在糖尿病肾病的发病中起着重要作用。核因子红细胞2相关因子2（Nrf 2）可以上调抗氧化基因的表达，保护细胞免受氧化损伤。本研究旨在检测Nrf 2表达调节对高糖诱导的小鼠系膜细胞氧化应激和Nrf 2靶向抗氧化剂表达的影响。在这项研究中，小鼠系膜细胞瞬时转染Nrf 2质粒或Nrf 2特异性siRNA。测定高糖诱导的细胞内ROS、丙二醛、细胞增殖和TGF-β 1分泌。测定小鼠系膜细胞中Nrf 2、血红素加氧酶-1（HO-1）、γ-谷氨酰半胱氨酸合成酶（γ-GCS）表达水平以及Nrf 2的核表达水平。我们发现高糖诱导小鼠系膜细胞产生ROS和丙二醛。诱导Nrf 2过表达可减少高糖诱导的小鼠系膜细胞ROS和丙二醛的产生，抑制细胞增殖和TGF-β 1的分泌，并上调HO-1和γ-GCS的表达。然而，敲低Nrf 2表达在小鼠系膜细胞中显示出相反的效果。这些结果表明，Nrf 2及其下游抗氧化剂HO-1和γ-GCS是高糖诱导的ROS相关小鼠系膜细胞功能障碍的负性调节剂。(C)2011 Elsevier Inc. All rights reserved.
Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic nephropathy. Nuclear factor erythroid 2-related factor 2 (Nrf2) can up-regulate the expression of antioxidant genes and protect cells from oxidative damage. The current study is aimed at examining the effect of modulation of Nrf2 expression on high glucose-induced oxidative stress and Nrf2-targeting antioxidant expression in mouse mesangial cells. In this study, mouse mesangial cells were transiently transfected with Nrf2-plasmid or the Nrf2-specific siRNA. The high glucose-induced intracellular ROS, malondialdehyde, cell proliferation, and TGF-beta 1 secretion were measured. The levels of Nrf2, heme oxygenase-1 (HO-1), gamma-glutamylcysteine synthethase (gamma-GCS) expression, and nuclear expression of Nrf2 in mouse mesangial cells were determined. We found that high glucose induced ROS and malondialdehyde generation in mouse mesangial cells. Induction of Nrf2 over-expression reduced the high glucose-induced ROS and malondialdehyde production, inhibited cell proliferation and TGF-beta 1 secretion, accompanied by up-regulating the expressions of HO-1 and gamma-GCS in mouse mesangial cells. However, knockdown of Nrf2 expression displayed reverse effects in mouse mesangial cells. All these results indicated that Nrf2 and its downstream antioxidants, HO-1 and gamma-GCS, are negative regulators of high glucose-induced ROS-related mouse mesangial cell dysfunction. (C) 2011 Elsevier Inc. All rights reserved.