title: The role of miR-146a on NF-κB expression level in human umbilical vein endothelial cells under hyperglycemic condition.
abstract: Emerging studies have been shown that the expression of micrRNA-146a (miR-146a, as a regulator of nuclear factor κB (NF-κB)), is changed in diabetic patients and animals. This study was designed to evaluate the possible role of miR-146a in the pathogenesis of diabetes-related microvascular complications. Concurrent with the creation of cellular hyperglycemia (25 mmol/L for 24 h), human umbilical vein endothelial cells (HUVECs) were transfected with 20 nmol/L of hsa-miR-146a antagomir or scramble using HiPerFect reagent (Qiagen). D-mannitol was used as osmotic control. Hyperglycemia increased the NF-κB gene expression and protein activity (as an inflammation index) in cultured HUVECs. Moreover, the gene expression level of miR-146a, and its target proteins, tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1) were increased under hyperglycemic condition. The knockdown of miR-146a by transfection of miR-146a antagomir notably increased the NF-κB activity and decreased the NF-κB mRNA in hyperglycemic HUVECs. Furthermore, miR-146a antagomir significantly increased IRAK1 and TRAF6 mRNA levels under hyperglycemic condition. These results demonstrate that the expression of miR-146a is upregulated in HUVECs during early phase of hyperglycemic condition possibly to regulate the NF-κB activity through inhibition of IRAK1 and TRAF6 (Fig. 4, Ref. 32).
authors.forename: K
authors.initials: K
authors.lastname: Kamali
authors.forename: E Salmani
authors.initials: ES
authors.lastname: Korjan
authors.forename: E
authors.initials: E
authors.lastname: Eftekhar
authors.forename: K
authors.initials: K
authors.lastname: Malekzadeh
authors.forename: F Ghadiri
authors.initials: FG
authors.lastname: Soufi
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D014162:Transfection
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: HUVECs; IRAK1; NF-κB; TRAF6.; hyperglycemia; miRNA-146a