MVP通過抑制IKK–NF-κB信號介導(dǎo)的炎癥來抑制肥胖和動脈粥樣硬化

中文摘要：

巨噬細胞主導(dǎo)的低度慢性炎癥在肥胖和動脈粥樣硬化中起著關(guān)鍵作用。然而，其潛在的調(diào)控機制仍未清楚。在此，我們發(fā)現(xiàn)主要斗篷蛋白（MVP），即獨特細胞核糖核蛋白顆粒的主要成分，是巨噬細胞中NF-κB信號通路的抑制因子。髓系特異性MVP基因敲除會加劇高脂飲食誘導(dǎo)的小鼠肥胖、胰島素抵抗、肝脂肪變性和動脈粥樣硬化。MVP缺陷導(dǎo)致的代謝紊亂惡化伴隨著微環(huán)境中巨噬細胞浸潤增加和炎癥反應(yīng)增強。體外研究顯示，MVP與TRAF6相互作用，阻止其招募到IRAK1并隨后發(fā)生寡聚化和泛素化。MVP及其α-螺旋結(jié)構(gòu)域的過表達抑制了TRAF6的活性并降低了巨噬細胞炎癥。我們的結(jié)果表明，巨噬細胞中的MVP是NF-κB信號通路的關(guān)鍵抑制因素，從而抑制代謝性疾病的發(fā)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.

論文信息：

論文題目：Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK–NF-κB signaling mediated inflammation

期刊名稱：Nature Communications

時間期卷：10, Article number:1801(2019)

在線時間：2019年4月17日

DOI： doi.org/10.1038/s41467-019-09588-x

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control liposomes

辦事處：Target Technology(靶點科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除 high-fat diet (HFD)高脂誘導(dǎo)的肥胖模型巨噬細胞，荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Nature Communications：MVP通過抑制IKK–NF-κB信號介導(dǎo)的炎癥來抑制肥胖和動脈粥樣硬化。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除肥胖模型巨噬細胞的材料和方法：

Monocyte recruitment assays

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.

材料和方法文獻截圖：