miR-221 is required for endothelial tip cell behaviors during vascular development.
miR-221 is required for endothelial tip cell behaviors during vascular development.
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DOI：
10.1016/j.devcel.2012.01.008
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发表时间：
2012-02-14
影响因子：
11.8
通讯作者：
Lawson, Nathan D.
中科院分区：
文献类型：
--
作者：
Nicoli, Stefania;Knyphausen, Carl-Philipp;Zhu, Lihua J.;Lakshmanan, Abirami;Lawson, Nathan D.
血管生成需要顶端和柄细胞之间不同细胞行为的协调。虽然这一过程是由血管内皮生长因子（VEGF）和Notch信号通路之间的相互作用调控，但对microRNA的潜在作用知之甚少。通过对斑马鱼进行深度测序和功能筛选，我们发现miR-221对血管生成至关重要。miR-221敲低表型缺陷与尖端细胞表达的Flt 4受体丢失相关。此外，miR-221是嵌合血管中尖端细胞增殖和迁移以及尖端细胞潜能所必需的。miR-221敲低还防止了与Notch缺陷相关的“过度血管生成”缺陷，并且miR-221表达被Notch信号传导抑制。最后，miR-221通过抑制两个靶点促进尖端细胞行为：细胞周期蛋白依赖性激酶抑制剂1b（cdkn 1b）和磷酸肌醇-3-激酶调节亚基1（pik 3r 1）。这些结果将miR-221鉴定为重要的调节节点，通过其在血管生成期间控制尖端细胞迁移和增殖。
Angiogenesis requires coordination of distinct cell behaviors between tip and stalk cells. While this process is governed by regulatory interactions between the Vascular endothelial growth factor (Vegf) and Notch signaling pathways, little is known about the potential role of microRNAs. Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis.
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影响因子：
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作者：
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