MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages
MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages
复制标题
MicroRNA-134 通过靶向 THP-1 巨噬细胞中的血管生成素样 4 来激活脂蛋白脂肪酶介导的脂质积累和炎症反应
DOI：
10.1016/j.bbrc.2015.10.158
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发表时间：
2016-04-08
影响因子：
3.1
通讯作者：
Tang, Chao-Ke
中科院分区：
文献类型：
--
作者：
Lan, Gang;Xie, Wei;Tang, Chao-Ke
血管生成素样蛋白4(Angiopoietin-like 4，ANGPTL4)是一种分泌型蛋白，是不可逆地抑制脂蛋白脂酶(LPL)活性的重要调节因子。巨噬细胞LPL通过脂蛋白和细胞表面受体之间的“分子桥”促进泡沫细胞的形成。据报道，巨噬细胞ANGPTL4通过抑制LPL活性、泡沫细胞的形成和炎症基因的表达来减缓动脉粥样硬化的发展。最近的一些研究表明，在动脉粥样硬化的巨噬细胞中，microRNA-134表达上调。在这里，我们证明了miR-134直接与ANGPTL4基因的3‘端非编码区结合来抑制ANGPTL4的表达。为了研究巨噬细胞miR-134的潜在作用，将miR-134模拟物或抑制剂导入THP-1巨噬细胞。我们的结果表明，LPL活性和蛋白质显著增加。我们还发现miR-134激活了LPL介导的脂质聚集。总之，我们的发现表明miR-134可能通过靶向ANGPTL4基因来调节巨噬细胞中的脂质积累和前炎性细胞因子的分泌。我们的研究结果也为动脉粥样硬化提供了一个有前景和潜在的治疗靶点。(C)2016 Elsevier Inc.保留所有权利。
Angiopoietin-like 4 (Angptl4), a secreted protein, is an important regulator to irreversibly inhibit lipoprotein lipase (LPL) activity. Macrophage LPL contributes to foam cell formation via a so-called"molecular bridge" between lipoproteins and receptors on cell surface. It has been reported that macrophage ANGPTL4 suppresses LPL activity, foam cell formation and inflammatory gene expression to reduce atherosclerosis development. Recently, some studies demonstrated that microRNA-134 is upregulated in atherosclerotic macrophages. Here we demonstrate that miR-134 directly binds to 3'UTR of ANGPTL4 mRNA to suppression the expression of ANGPTL4. To investigate the potential roles of macrophage miR-134, THP-1 macrophages were transfected with miR-134 mimics or inhibitors. Our results showed that LPL activity and protein were dramatically increased. We also found that miR-134 activated LPL-mediated lipid accumulation. Collectively, our findings indicate that miR-134 may regulate lipid accumulation and proinfiammatory cytokine secretion in macrophages by targeting the ANGPTL4 gene. Our results have also suggested a promising and potential therapeutic target for atherosclerosis. (C) 2016 Elsevier Inc. All rights reserved.