The impact of genetic manipulation of laminin and integrins at the blood-brain barrier.

The impact of genetic manipulation of laminin and integrins at the blood-brain barrier.
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DOI:
10.1186/s12987-022-00346-8
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发表时间:
2022-06-11
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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中枢神经系统(CNS)中的血管是独特的,具有高电阻和低渗透性,这产生了保护CNS内的敏感神经细胞免受血液中潜在有害成分影响的选择性屏障。这种血脑屏障(BBB)的分子基础存在于内皮粘附物和紧密连接蛋白复合物、血管基底膜(BM)的细胞外基质(ECM)组分以及邻近周细胞和星形胶质细胞终足的影响的水平。目前的证据支持这样的概念,即来自BBB ECM的指导性线索不仅对CNS血管的发育和成熟很重要,而且它们对于维持血管稳定性和BBB完整性也是必不可少的。在这篇综述中,我们研究了最丰富的ECM蛋白之一,层粘连蛋白的BBB完整性的贡献,并总结了不同的层粘连蛋白亚型或其整合素受体的基因缺失如何影响BBB的发展,成熟和稳定性。
Blood vessels in the central nervous system (CNS) are unique in having high electrical resistance and low permeability, which creates a selective barrier protecting sensitive neural cells within the CNS from potentially harmful components in the blood. The molecular basis of this blood–brain barrier (BBB) is found at the level of endothelial adherens and tight junction protein complexes, extracellular matrix (ECM) components of the vascular basement membrane (BM), and the influence of adjacent pericytes and astrocyte endfeet. Current evidence supports the concept that instructive cues from the BBB ECM are not only important for the development and maturation of CNS blood vessels, but they are also essential for the maintenance of vascular stability and BBB integrity. In this review, we examine the contributions of one of the most abundant ECM proteins, laminin to BBB integrity, and summarize how genetic deletions of different laminin isoforms or their integrin receptors impact BBB development, maturation, and stability.
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