PMID- 21637955 OWN - NLM STAT- MEDLINE DCOM- 20120501 LR - 20211020 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 39 IP - 2 DP - 2012 Feb TI - Aldose reductase regulates TNF-alpha-induced inducible nitric oxide synthase expression in human mesangial cells. PG - 1815-22 LID - 10.1007/s11033-011-0923-y [doi] AB - 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-alpha-induced (TNF-alpha-induced) iNOS expression in human mesangial cells (HMC) via nuclear factor kappaB (NFkappaB) signal pathway. The TNF-alpha-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-alpha 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 NFkappaB, 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-alpha in cultured HMC, indicating the novel function of AR in glomerulonephritis besides glucose metabolism. FAU - Zhao, Jingjing AU - Zhao J AD - Department of Pathology, Shanghai Medical School, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. 072101049@fudan.edu.cn FAU - Jiang, Tao AU - Jiang T FAU - Li, Hui AU - Li H FAU - Zhang, Yuejuan AU - Zhang Y FAU - Zhang, Nong AU - Zhang N LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110603 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.1.1.21 (Aldehyde Reductase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) SB - IM MH - Aldehyde Reductase/*metabolism MH - Blotting, Western MH - Cells, Cultured MH - Electrophoretic Mobility Shift Assay MH - Gene Expression Regulation, Enzymologic/genetics/*physiology MH - Glomerulonephritis/*metabolism MH - Humans MH - Mesangial Cells/*enzymology MH - NF-kappa B/metabolism MH - Nitric Oxide Synthase Type II/*metabolism MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 2011/06/04 06:00 MHDA- 2012/05/02 06:00 CRDT- 2011/06/04 06:00 PHST- 2010/03/14 00:00 [received] PHST- 2011/05/21 00:00 [accepted] PHST- 2011/06/04 06:00 [entrez] PHST- 2011/06/04 06:00 [pubmed] PHST- 2012/05/02 06:00 [medline] AID - 10.1007/s11033-011-0923-y [doi] PST - ppublish SO - Mol Biol Rep. 2012 Feb;39(2):1815-22. doi: 10.1007/s11033-011-0923-y. Epub 2011 Jun 3.