A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation
A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation
复制标题
DOI：
10.1073/pnas.2005924117
复制
发表时间：
2020-06-23
影响因子：
11.1
通讯作者：
Manabe, Ichiro
中科院分区：
文献类型：
--
作者：
Nakayama, Yukiteru;Fujiu, Katsuhito;Manabe, Ichiro
炎症的适当解决对于组织损伤后的稳态修复和恢复至关重要，并且其失调是各种非传染性疾病（如心血管和代谢疾病）的基础。巨噬细胞在整个初始炎症，其解决和组织修复中发挥着不同的作用。据报道，诱导和支持各种巨噬细胞活化状态需要差异代谢重编程。在此，我们发现一种长的非编码RNA（lncRNA）lncFAO通过促进巨噬细胞中的脂肪酸氧化（FAO）而有助于小鼠的炎症消退和组织修复。lncFAO在脂多糖（LPS）刺激培养的巨噬细胞后晚期被诱导，并且在消退和修复阶段期间在受损组织中的Ly6C hi单核细胞衍生的巨噬细胞中被诱导。我们发现lncFAO直接与线粒体三功能蛋白的HADHB亚基相互作用并激活FAO。IncFAO缺失损害与内毒素休克相关的炎症的消退，并延迟皮肤伤口中炎症的消退和组织修复。这些结果表明，通过调节线粒体代谢，lncFAO在炎症的消退和修复阶段充当巨噬细胞中免疫代谢控制的节点。
Proper resolution of inflammation is vital for repair and restora- tion of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovas- cular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA), lncFAO , con- tributes to inflammation resolution and tissue repair in mice by pro- moting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macro- phages and in Ly6C hi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs res- olution of inflammation related to endotoxic shock and delays reso- lution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.