title: Aldose reductase regulates TNF-α-induced inducible nitric oxide synthase expression in human mesangial cells.
abstract: Glomerulonephritis is one of the most important causes of renal failure, which is accompanied with production of Nitric Oxide (NO) synthesized by inducible nitric oxide synthase (iNOS). Aldose reductase (AR) is the key enzyme in polyol pathway and plays an important role in glucose metabolism. Here, we report our finding that AR regulates tumor-necrosis-factor-α-induced (TNF-α-induced) iNOS expression in human mesangial cells (HMC) via nuclear factor κB (NFκB) signal pathway. The TNF-α-induced iNOS expression in HMC with different level of AR was measured by Real-time PCR and Western blot. The activation of signal pathway was analyzed by Western blot and electrophoretic mobility shift assay (EMSA). In cultured HMC, TNF-α induces the expression of iNOS, which is attenuated by knockdown AR with siRNA. On the other side, transfection with pcDNA3.1-AR gets the consistent conclusion. Furthermore, knockdown of AR attenuated activity of NFκB, suggesting that the effects of AR on this pathway may result in the reduced iNOS transcription and expression. Taken together, these data demonstrate the role of AR in regulating iNOS expression induced by TNF-α in cultured HMC, indicating the novel function of AR in glomerulonephritis besides glucose metabolism.
authors.affiliation: Department of Pathology, Shanghai Medical School, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. 072101049@fudan.edu.cn
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nong
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D050527:Mesangial Cells / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000449:Aldehyde Reductase; D052247:Nitric Oxide Synthase Type II