Vascular endothelial growth factor induces endothelial fenestrations in vitro.
Vascular endothelial growth factor induces endothelial fenestrations in vitro.
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血管内皮生长因子在体外诱导内皮爆发。
DOI：
10.1083/jcb.140.4.947
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发表时间：
1998-02-23
影响因子：
7.8
通讯作者：
Risau, W
中科院分区：
文献类型：
--
作者：
Esser, S;Wolburg, K;Wolburg, H;Breier, G;Kurzchalia, T;Risau, W
抽象的。血管内皮生长因子（VEGF）是血管发生、血管生成和血管通透性的重要调节因子。与其在新血管形成期间的瞬时表达相反，VEGF及其受体在一些成人组织中持续且高度表达，例如肾小球和脉络丛。这表明这些组织的上皮细胞产生的VEGF可能参与表达VEGF受体的相邻内皮细胞中开窗的诱导或维持。在这里，我们描述了一个定义在体外培养系统中，窗孔形成诱导肾上腺皮质毛细血管内皮细胞的血管内皮生长因子，但不是由成纤维细胞生长因子。在内皮细胞与脉络丛上皮细胞或用VEGF 120或164的cDNA稳定转染的乳腺上皮细胞的共培养物中观察到内皮开窗的强烈诱导，但未用未转染的细胞。这些结果表明，在这些共培养物中，VEGF足以在体外诱导开窗。当上皮细胞被上皮来源的基底层型细胞外基质取代时，获得了相同的结果，但单独使用胶原蛋白则不行。在这个定义的系统中，VEGF介导的窗孔诱导总是伴随着融合的细胞膜小窝样囊泡数量的增加。在体内和体外，小窝，但不是窗，标记与小窝蛋白-1-特异性抗体。VEGF刺激导致VEGF受体酪氨酸磷酸化，但未观察到小窝蛋白-1的分布、磷酸化或蛋白水平的变化。我们的结论是，VEGF的存在下，基底层型细胞外基质特异性诱导内皮细胞开窗。这一定义的体外系统将允许进一步研究参与窗孔形成、小窝修饰和血管通透性的信号传导机制。
Abstract. Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis, angiogenesis, and vascular permeability. In contrast to its transient expression during the formation of new blood vessels, VEGF and its receptors are continuously and highly expressed in some adult tissues, such as the kidney glomerulus and choroid plexus. This suggests that VEGF produced by the epithelial cells of these tissues might be involved in the induction or maintenance of fenestrations in adjacent endothelial cells expressing the VEGF receptors. Here we describe a defined in vitro culture system where fenestrae formation was induced in adrenal cortex capillary endothelial cells by VEGF, but not by fibroblast growth factor. A strong induction of endothelial fenestrations was observed in cocultures of endothelial cells with choroid plexus epithelial cells, or mammary epithelial cells stably transfected with cDNAs for VEGF 120 or 164, but not with untransfected cells. These results demonstrate that, in these cocultures, VEGF is sufficient to induce fenestrations in vitro. Identical results were achieved when the epithelial cells were replaced by an epithelial-derived basal lamina-type extracellular matrix, but not with collagen alone. In this defined system, VEGF-mediated induction of fenestrae was always accompanied by an increase in the number of fused diaphragmed caveolae-like vesicles. Caveolae, but not fenestrae, were labeled with a caveolin-1–specific antibody both in vivo and in vitro. VEGF stimulation led to VEGF receptor tyrosine phosphorylation, but no change in the distribution, phosphorylation, or protein level of caveolin-1 was observed. We conclude that VEGF in the presence of a basal lamina-type extracellular matrix specifically induces fenestrations in endothelial cells. This defined in vitro system will allow further study of the signaling mechanisms involved in fenestrae formation, modification of caveolae, and vascular permeability.
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影响因子：
4.1
作者：
Birkenhager, R;Schneppe, B;McCarthy, JEG
通讯作者：
McCarthy, JEG
影响因子：
2.5
作者：
BREIER, G;CLAUSS, M;RISAU, W
通讯作者：
RISAU, W
影响因子：
3.9
作者：
COOMBER, BL;STEWART, PA;DELMAESTRO, RF
通讯作者：
DELMAESTRO, RF
DOI：
10.1097/00005072-198801000-00004
发表时间：
1988-01-01
影响因子：
3.2
作者：
COOMBER, BL;STEWART, PA;DELMAESTRO, RF
通讯作者：
DELMAESTRO, RF
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR