ABSTRACT

MALAT1 is associated with dendritic cells (DCs) maturation in Atherosclerosis (AS). This article aims to demystify the role of MALAT1 in AS. We separated immature DCs (iDCs) from healthy volunteers or ApoE-/- mice. And iDCs were treated with oxidized low density lipoprotein (ox-LDL) to induce DCs maturation. We found that ox-LDL promoted the levels of DCs maturation markers including CD83, CD86, IL-12 and IL-6. MALAT1 and NFIA were down-regulated, whereas miR-155-5p was up-regulated in the ox-LDL-treated iDCs. Furthermore, DCs maturation was notably suppressed by MALAT1 overexpression, NFIA overexpression or miR-155-5p knockdown. Moreover, MALAT1 functioned as a competing endogenous RNA to repress miR-155-5p, which controlled its down-stream target, NFIA. In addition, MALAT1 overexpression inhibited ox-LDL-stimulated DCs maturation by regulating miR-155-5p/NFIA axis. In AS mice, MALAT1 overexpression attenuated ox-LDL-stimulated DCs maturation and reduced atherosclerotic plaque area. In summary, our study demonstrates that MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated DCs maturation via miR-155-5p/NFIA axis. Thus, MALAT1/miR-155-5p/NFIA axis can potentially be used in the treatment of AS.

摘要

MALAT1 与动脉粥样硬化 (AS) 中树突状细胞 (DC) 的成熟有关。本文旨在揭开 MALAT1 在 AS 中的作用。我们将未成熟的 DC (iDC) 从健康志愿者或 ApoE-/- 小鼠中分离出来。并且用氧化低密度脂蛋白 (ox-LDL) 处理 iDCs 以诱导 DCs 成熟。我们发现ox-LDL促进了DCs成熟标志物的水平，包括CD83、CD86、IL-12和IL-6。MALAT1 和 NFIA 被下调，而 miR-155-5p 在 ox-LDL 处理的 iDC 中被上调。此外，MALAT1 过表达、NFIA 过表达或 miR-155-5p 敲低显着抑制了 DC 的成熟。此外，MALAT1 作为一种竞争性内源性 RNA 来抑制 miR-155-5p，后者控制着其下游靶标 NFIA。此外，MALAT1 过表达通过调节 miR-155-5p/NFIA 轴抑制 ox-LDL 刺激的 DCs 成熟。在 AS 小鼠中，MALAT1 过表达减弱了 ox-LDL 刺激的 DCs 成熟并减少了动脉粥样硬化斑块面积。总之，我们的研究表明，MALAT1 过表达通过 miR-155-5p/NFIA 轴抑制 ox-LDL 刺激的 DCs 成熟来减弱 AS。因此，MALAT1/miR-155-5p/NFIA 轴有可能用于治疗 AS。