HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.

HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
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DOI:
10.1038/ncomms4292
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发表时间:
2014-02-28
影响因子:
16.6
通讯作者:
Rye, Kerry-Anne
Rye, Kerry-Anne
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tabet, Fatiha;Vickers, Kasey C.;Torres, Luisa F. Cuesta;Wiese, Carrie B.;Shoucri, Bassem M.;Lambert, Gilles;Catherinet, Claire;Prado-Lourenco, Leonel;Levin, Michael G.;Thacker, Seth;Sethupathy, Praveen;Barter, Philip J.;Remaley, Alan T.;Rye, Kerry-Anne

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高密度脂蛋白(HDL)具有许多生物学功能,包括减少内皮活化和粘附分子表达。我们最近报道了 HDL 运输和传递功能性 microRNA (miRNA)。在这里,我们发现 HDL 通过将 miR-223 转移至内皮细胞来抑制细胞间粘附分子 1 (ICAM-1) 的表达。内皮细胞与 HDL 一起孵育后,内皮细胞中成熟的 miR-223 水平显着升高,而 HDL 则降低。然而,miR-223 在内皮细胞中不转录,并且在用来自 miR-223−/− 小鼠的 HDL 处理的细胞中不会增加。 HDL 抑制 ICAM-1 蛋白水平,但在用 miR-223 抑制剂预处理的细胞中则不然。 ICAM-1 是 HDL 转移的 miR-223 的直接靶标,这是细胞外 miRNA 调节非转录细胞中基因表达的第一个例子。总的来说,我们证明 HDL 的抗炎特性部分是通过内皮细胞中 HDL-miR-223 的传递和 ICAM-1 的翻译抑制而赋予的。
High-density lipoproteins (HDL) have many biological functions, including reducing endothelial activation and adhesion molecule expression. We recently reported that HDL transport and deliver functional microRNAs (miRNA). Here we show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1) through the transfer of miR-223 to endothelial cells. After incubation of endothelial cells with HDL, mature miR-223 levels are significantly increased in endothelial cells and decreased on HDL. However, miR-223 is not transcribed in endothelial cells and is not increased in cells treated with HDL from miR-223−/− mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR-223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is the first example of an extracellular miRNA regulating gene expression in cells where it is not transcribed. Collectively, we demonstrate that HDL’s anti-inflammatory properties are conferred, in part, through HDL-miR-223 delivery and translational repression of ICAM-1 in endothelial cells.
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