Syndecan-2 is essential for angiogenic sprouting during zebrafish development
Syndecan-2 is essential for angiogenic sprouting during zebrafish development
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DOI：
10.1182/blood-2003-06-1783
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发表时间：
2004-03-01
期刊：
影响因子：
20.3
通讯作者：
Ekker, SC
中科院分区：
文献类型：
--
作者：
Chen, E;Hermanson, S;Ekker, SC
我们使用基于吗啉基的基因靶向筛选来鉴定斑马鱼血管发育必需的新型蛋白质。我们发现 Syndecan-2（一种细胞表面硫酸乙酰肝素蛋白多糖）对于胚胎发生过程中的血管生成至关重要。 syndecan-2 的血管功能可能是保守的，因为斑马鱼和小鼠 syndecan-2 在主要干血管周围显示出相似的表达模式，而人 syndecan-2 可以恢复 syndecan-2 变形体的血管生成萌芽。相反，强制表达截短形式的 syndecan-2 会导致胚胎出现血管生成缺陷，这表明高度保守的细胞质尾部对于 syndecan-2 的血管功能很重要。我们通过斑马鱼的功能获得和功能丧失研究进一步表明，血管内皮生长因子 (VEGF) 和 syndecan-2 在体内存在遗传相互作用。 VEGF 介导的异位信号传导在 syndecan-2 morphant 中受到损害，异位 syndecan-2 会增强异位 VEGF 信号传导。 Syndecan-2 作为一种新型血管生成因子，是用于开发基于血管生成的疗法的潜在候选者。 (C) 2004 年，美国血液学会。
We used a morpholino-based gene-targeting screen to identify a novel protein essential for vascular development using the zebrafish, Danio rerio. We show that syndecan-2, a cell-surface heparan sulfate proteoglycan, is essential for angiogenic sprouting during embryogenesis. The vascular function of syndecan-2 is likely conserved, as zebrafish and mouse syndecan-2 show similar expression patterns around major trunk vessels, and human syndecan-2 can restore angiogenic sprouting in syndecan-2 morphants. In contrast, forced expression of a truncated form of syndecan-2 results in embryos with defects in angiogenesis, indicating that the highly conserved cytoplasmic tail is important for the vascular function of syndecan-2. We further show that vascular endothelial growth factor (VEGF) and syndecan-2 genetically interact in vivo using both gain-of-function and loss-of-function studies in zebrafish. VEGF-mediated ectopic signaling is compromised in syndecan-2 morphants, and ectopic syndecan-2 potentiates ectopic VEGF signaling. Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies. (C) 2004 by The American Society of Hematology.