Long non‐coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization
Long non‐coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization
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长非编码 RNA AK085865 消融通过调节巨噬细胞极化而导致对病毒性心肌炎的易感性
DOI：
10.1111/jcmm.15210
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发表时间：
2020
影响因子：
5.3
通讯作者：
Lv Kun
中科院分区：
文献类型：
--
作者：
Zhang Yingying;Li Xueqin;Kong Xiang;Zhang Mengying;Wang Deguo;Liu Yinhua;Lv Kun
越来越多的证据表明，巨噬细胞极化的调节剂可能在柯萨奇病毒B3（CVB 3）诱导的病毒性心肌炎（VM）的发展中发挥关键作用。然而，巨噬细胞极化的机制仍有待探讨。在这里，我们试图在巨噬细胞极化过程中识别新的和功能上重要的长非编码RNA（lncRNA），并研究它们的功能和对VM的贡献。在这项研究中，我们确定lncRNA AK 085865作为巨噬细胞极化的重要调节因子。AK 085865的敲低降低了M2巨噬细胞的表型表达，同时促进了向M1表型的极化。此外，AK 085865 −/−小鼠对CVB 3诱导的VM的易感性增加。我们观察到对M1巨噬细胞的显著偏倚，而在AK 085865 −/−VM小鼠中M2群体减少。总的来说，我们的研究结果揭示了AK 085865在体外和体内调节巨噬细胞极化中的关键作用，确定了VM发展中的新参与者，并提供了潜在的临床重要治疗靶点。
Accumulating evidence indicates that regulators of macrophage polarization may exert pivotal functions in the development of coxsackievirus B3 (CVB3)‐induced viral myocarditis (VM). However, the mechanisms underlying macrophage polarization remain to be explored. Here, we sought to identify novel and functionally important long non‐coding RNAs (lncRNAs) during macrophage polarization and to investigate their function and contribution to VM. In this study, we identified the lncRNA AK085865 as an important regulator of macrophage polarization. Knock‐down of AK085865 diminished phenotypical expression of M2 macrophages while promoting polarization to the M1 phenotype. Moreover, AK085865−/−mice had increased susceptibility to CVB3‐induced VM. We observed striking bias towards M1 macrophages, whereas the M2 population was decreased in AK085865−/−VM mice. Collectively, our findings uncover a critical role of AK085865 in the regulation of macrophage polarization in vitro and in vivo, identifying a new player in the development of VM and providing a potential clinically significant therapeutic target.