MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages
MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages
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MicroRNA-590 通过靶向人 THP-1 巨噬细胞中的脂蛋白脂肪酶基因来减少脂质积累和促炎细胞因子分泌。
DOI：
10.1016/j.biochi.2014.08.003
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发表时间：
2014-11-01
期刊：
影响因子：
3.9
通讯作者：
Tang, Chao-Ke
中科院分区：
文献类型：
--
作者：
He, Ping-Ping;Ouyang, Xin-Ping;Tang, Chao-Ke
背景：越来越多的证据表明，microRNA-590 （miR-590）对心血管疾病具有保护作用，但其机制尚不清楚。有趣的是，我们实验室和其他实验室之前的研究表明，巨噬细胞来源的脂蛋白脂肪酶（LPL）可能通过促进脂质积累和炎症反应来加速动脉粥样硬化。然而，microrna在转录后水平对LPL的调控尚不完全清楚。在本研究中，我们探讨了miR-590是否影响人THP-1巨噬细胞中LPL的表达及其对脂质积累和促炎细胞因子分泌的潜在后续影响。方法和结果：通过生物信息学分析和双荧光素酶报告基因分析，我们发现miR-590通过靶向LPL 3'UTR直接抑制LPL蛋白和mRNA的表达。LPL活性测定显示，miR-590降低了培养基中的LPL活性。油红0染色和高效液相色谱分析显示，miR-590对人THP-1巨噬细胞的脂质积累有抑制作用。我们还发现，通过ELISA检测，miR-590减轻了人THP-1巨噬细胞中促炎细胞因子的分泌。通过小干扰RNA的方法，我们发现LPL siRNA可以抑制miR-590抑制剂诱导的氧化ldl处理的人THP-1巨噬细胞脂质积累和促炎细胞因子分泌的增加。结论：MiR-590通过靶向人THP-1巨噬细胞的LPL基因，降低脂质积累和促炎细胞因子的分泌。因此，靶向miR-590可能提供一种治疗动脉粥样硬化性心血管疾病的有希望的策略。(C) 2014 Elsevier B.V.和法国生物化学与生物分子学会（SFBBM）。版权所有。
Background: Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages.Methods and results: Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red 0 staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages.Conclusions: MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases. (C) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved.