title: High glucose induces rat mesangial cells proliferation and MCP-1 expression via ROS-mediated activation of NF-κB pathway, which is inhibited by eleutheroside E.
abstract: 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-κB p65, p-NF-κB p65, IκBα, p-IκBα, IKKβ and p-IKKβ 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-κB, the degradation of IκBα and the expression of MCP-1. These results demonstrate that high glucose enhances MCs proliferation and MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by EE. Our findings provide a new perspective for the clinical treatment of DN.
authors.affiliation: a Department of Nephrology , Linyi People's Hospital , Linyi , P.R. China .
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: b Department of Endocrinology and Metabolism , The Affiliated Hospital of Qingdao University , Qingdao , P.R. China , and.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: c Department of Endocrinology , Linyi People's Hospital , Linyi , P.R. China.
authors.forename: Guanqi
authors.initials: G
authors.lastname: Gao
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics; D017705:Lignans / Q000008:administration & dosage*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005960:Glucosides; D020672:I-kappa B Proteins; D017705:Lignans; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C421885:eleutheroside E; D019255:NADPH Oxidases; D005947:Glucose
keywords: Cell proliferation; eleutheroside E; high glucose; mesangial cells; monocyte chemoattractant protein-1; nuclear factor kappa B; reactive oxygen species