Pericyte-to-endothelial cell signaling via vitronectin-integrin regulates blood-CNS barrier.
Pericyte-to-endothelial cell signaling via vitronectin-integrin regulates blood-CNS barrier.
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DOI：
10.1016/j.neuron.2022.02.017
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发表时间：
2022-05-18
期刊：
影响因子：
16.2
通讯作者：
Gu, Chenghua
中科院分区：
文献类型：
--
作者：
Ayloo, Swathi;Lazo, Christopher Gallego;Sun, Shenghuan;Zhang, Wei;Cui, Bianxiao;Gu, Chenghua
中枢神经系统（CNS）血管的内皮细胞构成血液-CNS屏障。屏障特性不是这些细胞固有的，而是由CNS微环境诱导和维持的。值得注意的是，CNS毛细血管的近腔表面被周细胞和星形胶质细胞包裹。然而，这些血管周围细胞的外在因素，调节屏障的完整性在很大程度上是未知的。在这里，我们建立玻连蛋白，由中枢神经系统周细胞分泌的细胞外基质蛋白，作为血液-中枢神经系统屏障功能的调节剂，通过与其整合素受体，α5在内皮细胞。玻连蛋白的基因消融或突变玻连蛋白以防止整合素结合以及整合素α5的内皮特异性缺失导致小鼠屏障渗漏。此外，玻连蛋白-整合素α5信号传导通过主动抑制内皮细胞中的胞吞转运来维持屏障完整性。这些结果表明，通过配体-受体相互作用从血管周围细胞到内皮细胞的信号传导是调节屏障通透性的关键机制。Ayloo等揭示了脑实质细胞如何积极维持血液-CNS屏障的机制。他们发现周细胞分泌的玻连蛋白及其内皮细胞受体整合素α5之间的配体-受体信号传导对于抑制转胞吞作用以确保小鼠屏障完整性至关重要。
Endothelial cells of blood vessels of the central nervous system (CNS) constitute blood-CNS barriers. Barrier properties are not intrinsic to these cells; rather they are induced and maintained by CNS microenvironment. Notably, the abluminal surface of CNS capillaries are ensheathed by pericytes and astrocytes. However, extrinsic factors from these perivascular cells that regulate barrier integrity are largely unknown. Here, we establish vitronectin, an extracellular-matrix protein secreted by CNS pericytes, as a regulator of blood-CNS barrier function via interactions with its integrin receptor, α5 in endothelial cells. Genetic ablation of vitronectin or mutating vitronectin to prevent integrin binding as well as endothelial-specific deletion of integrin α5 causes barrier leakage in mice. Furthermore, vitronectin-integrin α5 signaling maintains barrier integrity by actively inhibiting transcytosis in endothelial cells. These results demonstrate that signaling from perivascular cells to endothelial cells via ligand-receptor interactions is a key mechanism to regulate barrier permeability. Ayloo et al. reveal a mechanism of how blood-CNS barrier is actively maintained by brain parenchyma cells. They discovered a ligand-receptor signaling between pericyte-secreted vitronectin and its endothelial cell receptor integrin α5 is critical to suppress transcytosis to ensure barrier integrity in mice.
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影响因子：
19
作者：
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影响因子：
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作者：
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DOI：
10.1146/annurev-cellbio-100617-062608
发表时间：
2019-10-06
影响因子：
11.3
作者：
Langen UH;Ayloo S;Gu C
通讯作者：
Gu C