Journal
CELLULAR SIGNALLING
Volume 23, Issue 10, Pages 1625-1632Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2011.05.016
Keywords
Antioxidant; High glucose; Mesangial cells; Reactive oxygen species
Categories
Funding
- Hebei Provincial Nature Science Foundation of Chian Shijiazhuang Pharmaceutical Group Foundation, China [C2011206171]
- Hebei Provincial Nature Science Foundation, China [C2010000477]
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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.
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