Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis.
Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis.
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DOI：
10.1371/journal.pone.0008283
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发表时间：
2009-12-14
期刊：
影响因子：
3.7
通讯作者：
Ostrowski MC
中科院分区：
文献类型：
--
作者：
Srinivasan R;Zabuawala T;Huang H;Zhang J;Gulati P;Fernandez S;Karlo JC;Landreth GE;Leone G;Ostrowski MC
血管生成是由生长因子和细胞粘附两者协调的复杂过程，并且由血管基底膜的局灶性降解引发，随后是内皮细胞的迁移和增殖。Ras/Raf/MEK/ERK通路是血管生成过程中EC功能所必需的。尽管体外研究表明ERK 1和ERK 2参与内皮细胞存活，但它们在体内血管生成中的确切作用仍不清楚。Cre/loxP技术用于在小鼠发育过程中在内皮细胞中抑制Erk 1和Erk 2，由于血管生成严重减少而导致胚胎死亡。原代内皮细胞中Erk 1和Erk 2的缺失导致细胞增殖和迁移减少，但不增加细胞凋亡。在双基因敲除细胞中，关键细胞周期调节因子的表达减少，在胚胎发生过程中可以观察到内皮细胞中DNA合成减少。有趣的是，桩蛋白和粘着斑激酶在体内和体外缺乏Erk 1和Erk 2的内皮细胞中均以较低水平表达，导致细胞骨架组织和细胞运动性的缺陷。桩蛋白和粘着斑激酶表达的调节发生在转录后。这些结果表明，ERK 1和ERK 2协调血管生成过程中内皮细胞的增殖和迁移。
Angiogenesis is a complex process orchestrated by both growth factors and cell adhesion and is initiated by focal degradation of the vascular basement membrane with subsequent migration and proliferation of endothelial cells. The Ras/Raf/MEK/ERK pathway is required for EC function during angiogenesis. Although in vitro studies implicate ERK1 and ERK2 in endothelial cell survival, their precise role in angiogenesis in vivo remains poorly defined. Cre/loxP technology was used to inactivate Erk1 and Erk2 in endothelial cells during murine development, resulting in embryonic lethality due to severely reduced angiogenesis. Deletion of Erk1 and Erk2 in primary endothelial cells resulted in decreased cell proliferation and migration, but not in increased apoptosis. Expression of key cell cycle regulators was diminished in the double knockout cells, and decreased DNA synthesis could be observed in endothelial cells during embryogenesis. Interestingly, both Paxillin and Focal Adhesion Kinase were expressed at lower levels in endothelial cells lacking Erk1 and Erk2 both in vivo and in vitro, leading to defects in the organization of the cytoskeleton and in cell motility. The regulation of Paxillin and Focal Adhesion Kinase expression occurred post-transcriptionally. These results demonstrate that ERK1 and ERK2 coordinate endothelial cell proliferation and migration during angiogenesis.
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在两种血管生成途径中，差异alphav整联蛋白介导的RAS-ERK信号传导。
DOI：
10.1083/jcb.200304105
发表时间：
2003-09-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hood JD;Frausto R;Kiosses WB;Schwartz MA;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
9.2
作者：
Giroux, S;Tremblay, M;Charron, J
通讯作者：
Charron, J
DOI：
10.1073/pnas.0507399103
发表时间：
2006-01-31
影响因子：
11.1
作者：
Galabova-Kovacs, G;Matzen, D;Baccarini, M
通讯作者：
Baccarini, M
影响因子：
4.8
作者：
Avraham, HK;Lee, TH;Avraham, S
通讯作者：
Avraham, S
影响因子：
4.8
作者：
Liu, ZX;Yu, CF;Cantley, LG
通讯作者：
Cantley, LG