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首页> 外文期刊>Cell and Tissue Research >The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions.
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The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions.

机译：硫酸乙酰肝素蛋白聚糖凝集素通过稳定粘附连接而有助于小鼠脑内皮细胞的屏障特性。

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摘要

Barrier characteristics of brain endothelial cells forming the blood-brain barrier (BBB) are tightly regulated by cellular and acellular components of the neurovascular unit. During embryogenesis, the accumulation of the heparan sulfate proteoglycan agrin in the basement membranes ensheathing brain vessels correlates with BBB maturation. In contrast, loss of agrin deposition in the vasculature of brain tumors is accompanied by the loss of endothelial junctional proteins. We therefore wondered whether agrin had a direct effect on the barrier characteristics of brain endothelial cells. Agrin increased junctional localization of vascular endothelial (VE)-cadherin, β-catenin, and zonula occludens-1 (ZO-1) but not of claudin-5 and occludin in the brain endothelioma cell line bEnd5 without affecting the expression levels of these proteins. This was accompanied by an agrin-induced reduction of the paracellular permeability of bEnd5 monolayers. In vivo, the lack of agrin also led to reduced junctional localization of VE-cadherin in brain microvascular endothelial cells. Taken together, our data support the notion that agrin contributes to barrier characteristics of brain endothelium by stabilizing the adherens junction proteins VE-cadherin and β-catenin and the junctional protein ZO-1 to brain endothelial junctions.
机译：形成血脑屏障（BBB）的脑内皮细胞的屏障特性受到神经血管单元的细胞和脱细胞成分的严格调控。在胚胎发生过程中，硫酸乙酰肝素蛋白聚糖凝集素在包埋脑血管的基底膜中的积累与BBB的成熟有关。相反，在脑肿瘤的脉管系统中凝集素沉积的损失伴随着内皮连接蛋白的损失。因此，我们想知道凝集素是否对脑内皮细胞的屏障特性有直接影响。 Agrin可增加脑内皮细胞瘤细胞bEnd5中血管内皮（VE）-钙黏着蛋白，β-连环蛋白和小带闭合蛋白1（ZO-1）的结合定位，但不增加claudin-5和闭合蛋白的连接定位，而不会影响这些蛋白的表达水平。这伴随着凝集素诱导的bEnd5单层细胞旁通透性的降低。在体内，缺乏凝集素还导致脑微血管内皮细胞中VE-钙黏着蛋白的连接定位降低。综上所述，我们的数据支持以下观点：凝集素通过稳定粘附连接蛋白VE-cadherin和β-catenin以及连接蛋白ZO-1到脑内皮连接而有助于大脑内皮的屏障特性。

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