title: Modulation of Nrf2 expression alters high glucose-induced oxidative stress and antioxidant gene expression in mouse mesangial cells.
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.
authors.affiliation: Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Fuxu
authors.initials: F
authors.lastname: Wang
authors.forename: Lianshan
authors.initials: L
authors.lastname: Zhang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D004151:Dipeptides / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D004151:Dipeptides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D005947:Glucose; C017341:gamma-glutamylcysteine