Lipocalin-2 enhances angiogenesis in rat brain endothelial cells via reactive oxygen species and iron-dependent mechanisms.

Lipocalin-2 enhances angiogenesis in rat brain endothelial cells via reactive oxygen species and iron-dependent mechanisms.
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DOI:
10.1111/jnc.13023
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发表时间:
2015-03
影响因子:
4.7
通讯作者:
Xing C
Xing C
中科院分区:
医学2区
文献类型:
--
作者:
Wu L;Du Y;Lok J;Lo EH;Xing C

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炎症是中枢神经系统病理生理学的重要组成部分。然而,炎症因子现在被认为既有好处也有坏处。在这里,我们检验了一种假设,即Lipocalin-2,一种可以在受损的中枢神经系统中上调的炎性分子,可能会促进脑血管内皮细胞的血管生成。在RBE.4大鼠脑内皮细胞中加入Lipocalin-2(0.5-2.0微克/毫升)可显著增加基质细胞管的形成和划痕迁移,并增加铁和活性氧(ROS)的水平。自由基清除剂(UE83836E)、NOx抑制剂(Apocynin)和铁络合剂(去铁酮)的联合治疗显著抑制了Lipocalin-2促进脑内皮细胞管形成和划痕迁移的能力。这些发现为Lipocalin-2可以通过铁和ROS相关途径促进血管生成的概念提供了体外证据,并支持了Lipocalin-2可能有助于炎症的神经血管恢复的观点。
Inflammation is a key part of central nervous system pathophysiology. However, inflammatory factors are now thought to have both beneficial and deleterious effects. Here, we examine the hypothesis that lipocalin-2, an inflammatory molecule that can be upregulated in the distressed central nervous system, may enhance angiogenesis in brain endothelial cells. Adding lipocalin-2 (0.5–2.0µg/ml) to RBE.4 rat brain endothelial cells significantly increased matrigel tube formation and scratch migration, and also elevated levels of iron and reactive oxygen species (ROS). Co-treatment with a radical scavenger (UE83836E), a Nox inhibitor (apocynin) and an iron chelating agent (deferiprone) significantly dampened the ability of lipocalin-2 to enhance tube formation and scratch migration in brain endothelial cells. These findings provide in vitro proof of the concept that lipocalin-2 can promote angiogenesis via iron- and ROS-related pathways, and support the idea that lipocalin-2 may contribute to the neurovascular recovery aspects of inflammation.
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