PMID- 26644089 OWN - NLM STAT- MEDLINE DCOM- 20161114 LR - 20171116 IS - 1532-4281 (Electronic) IS - 1079-9893 (Linking) VI - 36 IP - 2 DP - 2016 TI - High glucose induces rat mesangial cells proliferation and MCP-1 expression via ROS-mediated activation of NF-kappaB pathway, which is inhibited by eleutheroside E. PG - 152-7 LID - 10.3109/10799893.2015.1061002 [doi] AB - Glomerular hypertrophy and extracellular matrix accumulation are early features of diabetic nephropathy (DN). High glucose-induced oxidative stress is implicated in the etiology of DN. This study aims to investigate the effect of eleutheroside E (EE) on high glucose mediated rat mesangial cells (MCs) proliferation and monocyte chemoattractant protein-1 (MCP-1) expression and the underlying mechanism. MCs proliferation was assessed by MTT assay. Reactive oxygen species (ROS) level and MCP-1 expression were evaluated by ELISA kit. The protein expression of p47, NF-kappaB p65, p-NF-kappaB p65, IkappaBalpha, p-IkappaBalpha, IKKbeta and p-IKKbeta were determined by Western blot. The results showed that treatment with EE markedly attenuated high glucose induced MCs proliferation and in a dose-dependent manner. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. Meanwhile, EE administration could effectively alleviate the high glucose-stimulated activation of NF-kappaB, the degradation of IkappaBalpha and the expression of MCP-1. These results demonstrate that high glucose enhances MCs proliferation and MCP-1 expression by activating the ROS/NF-kappaB pathway and can be inhibited by EE. Our findings provide a new perspective for the clinical treatment of DN. FAU - Yang, Xiuqin AU - Yang X AD - a Department of Nephrology , Linyi People's Hospital , Linyi , P.R. China . FAU - Wang, Yangang AU - Wang Y AD - b Department of Endocrinology and Metabolism , The Affiliated Hospital of Qingdao University , Qingdao , P.R. China , and. FAU - Gao, Guanqi AU - Gao G AD - c Department of Endocrinology , Linyi People's Hospital , Linyi , P.R. China. LA - eng PT - Journal Article DEP - 20151207 PL - England TA - J Recept Signal Transduct Res JT - Journal of receptor and signal transduction research JID - 9509432 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Glucosides) RN - 0 (I-kappa B Proteins) RN - 0 (Lignans) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (Transcription Factor RelA) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 8JP2P44H3Z (eleutheroside E) RN - EC 1.6.3.- (NADPH Oxidases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Proliferation/drug effects MH - Chemokine CCL2/*biosynthesis/genetics MH - Diabetic Nephropathies/*drug therapy/genetics/pathology MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects MH - Glucose/administration & dosage MH - Glucosides/*administration & dosage MH - Humans MH - I-kappa B Proteins/biosynthesis/genetics MH - Lignans/*administration & dosage MH - Mesangial Cells/*drug effects/metabolism/pathology MH - NADPH Oxidases/biosynthesis/genetics MH - NF-KappaB Inhibitor alpha MH - NF-kappa B/*biosynthesis/genetics MH - Rats MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - Transcription Factor RelA/biosynthesis/genetics OTO - NOTNLM OT - Cell proliferation OT - eleutheroside E OT - high glucose OT - mesangial cells OT - monocyte chemoattractant protein-1 OT - nuclear factor kappa B OT - reactive oxygen species EDAT- 2015/12/09 06:00 MHDA- 2016/11/15 06:00 CRDT- 2015/12/09 06:00 PHST- 2015/12/09 06:00 [entrez] PHST- 2015/12/09 06:00 [pubmed] PHST- 2016/11/15 06:00 [medline] AID - 10.3109/10799893.2015.1061002 [doi] PST - ppublish SO - J Recept Signal Transduct Res. 2016;36(2):152-7. doi: 10.3109/10799893.2015.1061002. Epub 2015 Dec 7.