Cooperative interaction of angiopoietin-like proteins 1 and 2 in zebrafish vascular development
Cooperative interaction of angiopoietin-like proteins 1 and 2 in zebrafish vascular development
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DOI：
10.1073/pnas.0501902102
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发表时间：
2005-09-20
影响因子：
11.1
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Kubota, Y;Oike, Y;Suda, T
血管生成素样蛋白（Angptl）1和Angptl 2被认为是孤儿配体，它们高度同源，特别是在含有推定受体结合位点的纤维蛋白原样结构域中。这种相似性表明这两种蛋白质之间的潜在合作功能。本研究利用Morpholino反义技术对斑马鱼Angptl 1和Angptl 2基因的功能进行了分析。Angptl 1和Angptl 2两者的敲低由于在萌芽阶段内皮细胞的凋亡增加而产生严重的血管缺陷。体外研究表明，Angptl 1和Angptl 2通过磷脂酰肌醇3-激酶/Akt途径具有抗凋亡活性，并且共注射组成性活性Akt/蛋白激酶B mRNA挽救了双敲低胚胎中观察到的受损血管发育。这些结果提供了一个生理的证据，合作的相互作用，血管生成素11和血管生成素12在血管内皮细胞通过磷脂酰肌醇3-激酶/Akt介导的抗凋亡活性。
Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase/Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in enclothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.