中文摘要：
巨噬细胞主导的低度慢性炎症在肥胖和动脉粥样硬化中起着关键作用。然而，其潜在的调控机制仍未清楚。在此，我们发现主要斗篷蛋白（MVP），即独特细胞核糖核蛋白颗粒的主要成分，是巨噬细胞中NF-κB信号通路的抑制因子。髓系特异性MVP基因敲除会加剧高脂饮食诱导的小鼠肥胖、胰岛素抵抗、肝脂肪变性和动脉粥样硬化。MVP缺陷导致的代谢紊乱恶化伴随着微环境中巨噬细胞浸润增加和炎症反应增强。体外研究显示，MVP与TRAF6相互作用，阻止其招募到IRAK1并随后发生寡聚化和泛素化。MVP及其α-螺旋结构域的过表达抑制了TRAF6的活性并降低了巨噬细胞炎症。我们的结果表明，巨噬细胞中的MVP是NF-κB信号通路的关键抑制因素，从而抑制代谢性疾病的发展。
英文摘要：
Macrophage-orchestrated, low-grade chronic inflammation plays a pivotal role in obesity and atherogenesis. However, the underlying regulatory mechanisms remain incompletely understood. Here, we identify major vault protein (MVP), the main component of unique cellular ribonucleoprotein particles, as a suppressor for NF-κB signaling in macrophages. Both global and myeloid-specific MVP gene knockout aggravates high-fat diet induced obesity, insulin resistance, hepatic steatosis and atherosclerosis in mice. The exacerbated metabolic disorders caused by MVP deficiency are accompanied with increased macrophage infiltration and heightened inflammatory responses in the microenvironments. In vitro studies reveal that MVP interacts with TRAF6 preventing its recruitment to IRAK1 and subsequent oligomerization and ubiquitination. Overexpression of MVP and its α-helical domain inhibits the activity of TRAF6 and suppresses macrophage inflammation. Our results demonstrate that macrophage MVP constitutes a key constraint of NF-κB signaling thereby suppressing metabolic diseases.
论文信息：
论文题目：Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK–NF-κB signaling mediated inflammation
期刊名称：Nature Communications
时间期卷：10, Article number:1801(2019)
在线时间：2019年4月17日
DOI： doi.org/10.1038/s41467-019-09588-x
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除 high-fat diet (HFD)高脂诱导的肥胖模型巨噬细胞，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications：MVP通过抑制IKK–NF-κB信号介导的炎症来抑制肥胖和动脉粥样硬化。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肥胖模型巨噬细胞的材料和方法：
For the monocyte infiltration into atherosclerotic lesion assay, experimental male mice were fed a WD for 10 weeks. Clodronate-liposomes (250 μl, Liposoma) were i.v. injected in order to transiently deplete monocytes, followed by i.v. injection of 250 μl fluorescent microspheres 48 h later. Fluoresbrite FITC-dyed (YG, 0.5 μm) plain microspheres (2.5% solids [w/v]; Polysciences) were diluted 1:25 in PBS. Mice were euthanized and hearts with aortic root was then used for consecutive sections from the atrioventricular valve at a thickness of 20 μm. Nuclei were counter-stained by DAPI Fluor mount-G (SouthernBiotech). Images were then captured using a fluorescence microscope (Carl Zeiss). Beads that reflect monocyte recruitment were quantified in 3–5 aortic sinus sections per mouse.
材料和方法文献截图：
