Sohet Fabien, Lin Christina, Munji Roeben N, Lee Seo Yeon, Ruderisch Nadine, Soung Allison, Arnold Thomas D, Derugin Nikita, Vexler Zinaida S, Yen Frances T, Daneman Richard
Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093
Department of Anatomy, Department of Pediatrics, and Department of Neurology, University of California, San Francisco, San Francisco, CA 94143.
J Cell Biol. 2015 Mar 16;208(6):703-11. doi: 10.1083/jcb.201410131. Epub 2015 Mar 9.
The blood-brain barrier (BBB) is a term used to describe the unique properties of central nervous system (CNS) blood vessels. One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs). Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues. We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis. We further demonstrate that the BBB does not seal during embryogenesis in Lsr knockout mice with a leakage to small molecules. Finally, in mouse models in which BBB was disrupted, including an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and a middle cerebral artery occlusion (MCAO) model of stroke, LSR was down-regulated, linking loss of LSR and pathological BBB leakage.
血脑屏障（BBB）是一个用于描述中枢神经系统（CNS）血管独特特性的术语。血脑屏障的一个重要特性是由中枢神经系统内皮细胞（ECs）之间的紧密连接（TJs）形成的细胞旁屏障。在此，我们表明，脂解刺激脂蛋白受体（LSR）作为在三个细胞膜交汇点处细胞旁连接的一个组成部分，与其他非神经组织中的内皮细胞相比，在中枢神经系统内皮细胞中大量富集。我们证明LSR在三细胞连接处特异性表达，并且其表达与胚胎发育过程中血脑屏障形成的起始相关。我们进一步证明，在Lsr基因敲除小鼠的胚胎发育过程中，血脑屏障不会封闭，小分子会发生渗漏。最后，在血脑屏障被破坏的小鼠模型中，包括多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）模型和中风的大脑中动脉闭塞（MCAO）模型，LSR表达下调，这表明LSR的缺失与病理性血脑屏障渗漏有关。
