title: Regulation of microRNA-155 in endothelial inflammation by targeting nuclear factor (NF)-κB P65.
abstract: Increasing evidences have illuminated the fundamental role of inflammation in mediating all stages of atherosclerosis. miR-155, a typical multi-functional miRNA, has recently emerged as a novel component of inflammatory signal transduction in the pathogenesis of atherosclerosis. However, little is known about whether endothelial highly expressed miR-155 can regulate endothelial inflammation-related transcription factors and the predicted role of miR-155 as a negative feedback regulator in endothelial inflammation involved in atherosclerosis. Bioinformatics analysis showed that RELA (nuclear factor-κB p65) is a potential target gene of miR-155 and this was confirmed by a luciferase reporter assay. Our results show that microRNA-155 mediate endothelial inflammation and decrease NFкB p65 and adhesion molecule expression in TNFα-stimulated endothelial cells. Transfection with miR-155 significantly inhibited TNFα-induced monocyte adhesion to endothelium. Inhibition of miR-155 enhanced p65 level and endothelial inflammatory response which was counteracted through the depletion of P65 by Si-P65. On the other hand, knockdown of eNOS, another target of miR-155, while transfecting with miR-155 inhibitor resulted in more significant inflammatory response. miR-155 is highly expressed in TNFα treated HUVECs, deprived of endogenous p65 could reverse TNFα-induced upregulation of miR-155. Thus, TNFα induced miR-155 may serve as a negative feedback regulator in endothelial inflammation involved in atherosclerosis by targeting nuclear transcription factor P65. These results provide a rationale for intervention of intracellular microRNA as possible anti-atherosclerotic targets.
authors.affiliation: Division of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Fan
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.forename: Gui-Fu
authors.initials: GF
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D016207:Cytokines / Q000378:metabolism; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha
keywords: ENDOTHELIAL INFLAMMATION; NFкB P65; TNFα; microRNA 155