miR-146a-3p targeted RELB to regulate cytokine secretion in endothelial cells of atherosclerotic mice

Objective:To explore how miR-146a-3p can regulate the cytokine secretion of endothelial cells in atherosclerotic mice through the nuclear factorκB subunit(RELB).Methods:Apolipoprotein knockout(ApoE-/-)mouse atherosclerosis model was established by feeding program of high-fat diet formula and vascular endothelial cells were performed on primary culture.The difference in expression levels of miR-146a-3p in endothelial tissues of atherosclerotic mice and control mice was detected by real-time fluorescence quantitative PCR.The match between mir-146a-3p and RelB was analyzed by TargetScanHuman.Then whether miR-146a-3p targeted RELB was checked by luciferase reporter system.In the case of miR-146a-3p mimics overexpression or miR-146a-3p inhibitor knockdown,the granulocyte colony stimulating factor(GCSF),the levels of granulocyte macrophage colony stimulating factor(GM-CSF),interleukin 2(IL-2),interleukin 3(IL-3),interleukin 4(IL-4),interleukin 5(IL-5),interleukin 6(IL-6),interleukin 9(IL-9),interleukin 10(IL-10),interleukin 12 p40(IL-12 p40),interleukin 12 p70(IL-12 p70),interleukin 13(IL-13),interleukin 17(IL-17),interferon gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),monocyte chemoattractant protein 5(MCP-5),small inducible cytokine A5(RANTES),and tumor necrosis factor-α(TNFα)were detected by enzyme-linked immunosorbent assay.Results:Compared with the control group,the expression of miR-146a-3p in vascular endothelial tissue of atherosclerotic mice was reduced(P<0.05);MiR-146a-3p targeted the 3'UTR of RELB;After overexpression of miR-520a-3p,the expression level of RELB was decreased,and the levels of GCSF,GM-CSF,IL-2,IL-3,IL-4,IL-5,IL-6,IL-9,IL-10,IL-12 p40,IL-12 p70,IL-13,IL-17,IFN-γ,MCP-1,MCP-5,RANTES,and TNFαcytokines secreted by endothelial cells in atherosclerotic mice were decreased(P<0.05);After knocking down miR-520a-3p,the expression level of RELB was increased,and the levels of GCSF,GM-CSF,IL-2,IL-3,IL-4,IL-5,IL-6,IL-9,IL-10,IL-12 p40,IL-12 p70,IL-13,IL-17,IFN-γ,MCP-1,MCP-5,RANTES,and TNFαcytokines secreted by endothelial cells in atherosclerotic mice were increased(P<0.05).Conclusion:MiR-146a-3p inhibited the cytokine secretion of vascular endothelial cells in atherosclerotic mice by targeting the key molecule of nuclear factorκB(NF-kB)signaling pathway RELB.