Modulation of Nrf2 expression alters high glucose-induced oxidative stress and antioxidant gene expression in mouse mesangial cells |
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Authors: | Li Hang Wang Fuxu Zhang Lianshan Cao Yanping Liu Wei Hao Jun Liu Qingjuan Duan Huijun |
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Institution: | a Department of Histology and Embryology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Chinab Department of Pathology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Chinac Department of Hematology, the Second Affiliated Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang 050000, Chinad Department of Pathology, Traditional Medicine Hospital of Hebei Province, 369 East Zhongshan Road, Shijiazhuang 050011, China |
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Abstract: | 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-β1 secretion were measured. The levels of Nrf2, heme oxygenase-1 (HO-1), γ-glutamylcysteine synthethase (γ-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-β1 secretion, accompanied by up-regulating the expressions of HO-1 and γ-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 γ-GCS, are negative regulators of high glucose-induced ROS-related mouse mesangial cell dysfunction. |
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Keywords: | ROS reactive oxygen species Nrf2 nuclear factor erythroid 2-related factor 2 HO-1 heme oxygenase-1 γ-GCS γ-glutamylcysteine synthethase |
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