Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro
Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro
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DOI：
10.1016/s0165-3806(01)00220-6
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发表时间：
2001-09-23
期刊：
影响因子：
--
通讯作者：
Madri, JA
中科院分区：
文献类型：
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作者：
Chow, J;Ogunshola, O;Madri, JA
慢性亚致死性缺氧与神经血管行为的改变有关，这种改变在一定程度上是通过诱导血管内皮生长因子A(VEGF-A)(165)介导的。在本报告中，我们证明了当培养RBE4细胞(来源于啮齿动物脑微血管)时，在三维胶原凝胶中：(1)以剂量依赖的方式诱导血管内皮生长因子A(165)诱导增加管状细胞的形成；(2)在轻度缺氧条件下诱导细胞凋亡；(3)通过在剂量依赖的可抑制的水槽中添加外源血管内皮生长因子-A(165)或与原代新生大鼠星形胶质细胞共同培养，可以从缺氧的影响中解救出来，在低氧条件下诱导星形胶质细胞表达增加的血管内皮生长因子-A。进一步，我们证明：(4)观察到的星形胶质细胞产生的，血管内皮生长因子介导的抗凋亡保护(存活)是可被可溶性重组血管内皮生长因子受体-1(SFlt)抑制的，并与MAPK酪氨酸磷酸化的强烈诱导有关。这些发现说明了血管内皮生长因子在神经血管存活过程中的重要性，以应对发育中的脑损伤，并为深入了解相关的信号通路提供了线索。(C)2001 Elsevier Science B.V.保留所有权利。
Chronic sublethal hypoxia has been associated with changes in neurovascular behavior, mediated, in part, by induction of vascular endothelial growth factor-A (VEGF-A(165)). In this report we demonstrate that RBE4 cells (derived from rodent cerebral microvasculature), when cultured in three-dimensional collagen gels: (1) Are induced to undergo increased tube formation in response to VEGF-A(165) in a dose-dependent manner; (2) undergo apoptosis under mild hypoxic conditions; (3) are rescued from the effects of hypoxia by the addition of exogenous VEGF-A(165) in a dose-dependent and inhibitable mariner or by co-culture with primary newborn rat astrocytes, which are induced to express increased amounts of VEGF-A in hypoxic conditions. Further, we demonstrate that: (4) The observed astrocyte produced, VEGF-mediated protection from apoptosis (survival) is inhibitable with soluble recombinant VEGF receptor-1 (sFlt), and is associated with a robust induction of MAPK tyrosine phosphorylation. These findings illustrate the importance of VEGF in the process of neurovascular survival in response to injury in developing brain and provide insight into the signaling pathways involved. (C) 2001 Elsevier Science B.V. All rights reserved.