Pericytes regulate the blood-brain barrier
Pericytes regulate the blood-brain barrier
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DOI：
10.1038/nature09522
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发表时间：
2010-11-25
期刊：
影响因子：
64.8
通讯作者：
Betsholtz, Christer
中科院分区：
文献类型：
--
作者：
Armulik, Annika;Genove, Guillem;Betsholtz, Christer
血脑屏障(BBB)由特定的物理屏障、酶和转运蛋白组成，它们共同维持中枢神经系统(CNS)必要的细胞外环境(1)。主要的物理屏障是在中枢神经系统内皮细胞中发现的，依赖于紧密连接的连续复合体和减少的囊泡运输(2)。血脑屏障的其他可能成分包括细胞外基质、星形胶质细胞和周细胞(3)，但这些不同成分对血脑屏障的相对贡献在很大程度上仍不清楚(1，3)。在这里，我们展示了周细胞在体内血脑屏障中的直接作用。使用一组成体可存活的周细胞缺陷小鼠突变体，我们表明周细胞缺陷增加了血脑屏障对水和一系列低分子质量和高分子质量示踪剂的渗透性。通透性的增加是通过内皮细胞穿透发生的，这一过程被药物伊马替尼迅速阻止。此外，我们发现周细胞至少通过两种方式在血脑屏障发挥作用：通过调节内皮细胞中血脑屏障特异的基因表达模式，以及通过诱导中枢神经系统血管周围星形胶质细胞末端足部的极化。我们的结果表明，周细胞在神经血管单位内皮细胞和星形胶质细胞功能的整合以及血脑屏障的调节中起着新的和关键的作用。
The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS)(1). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport(2). Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes(3), but the relative contribution of these different components to the BBB remains largely unknown(1,3). Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.