FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.
FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.
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FOXP1通过抑制内皮细胞中的抑制性引导蛋白含量5B来刺激血管生成。
DOI：
10.1371/journal.pone.0070873
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moser M
中科院分区：
文献类型：
--
作者：
Grundmann S;Lindmayer C;Hans FP;Hoefer I;Helbing T;Pasterkamp G;Bode C;de Kleijn D;Moser M
叉头盒 (Fox) 转录因子是心血管发育的重要调节因子，最近已证明几种 Fox 蛋白可调节胚胎和产后血管生成。然而，在心血管组织中高表达的FoxP亚家族的作用迄今尚未被研究。在这里，我们发现转录因子 FoxP1 是内皮细胞中表达最高的 FoxP 蛋白，并且在小鼠后肢缺血期间，它在新生血管形成部位上调。 FoxP1 的沉默导致对培养的内皮细胞的增殖、管形成和迁移的强烈抑制。因此，在斑马鱼中敲除 FoxP1 后，体节间血管形成就会受到破坏。通过基因表达谱分析，我们发现 FoxP1 诱导内皮转录组发生特异性变化，并作为信号蛋白 5B 的抑制剂发挥作用，信号蛋白 5B 先前被描述为神经元抑制因子。我们的研究结果表明，semaphorin 5B 还可以作为内皮细胞增殖、迁移和发芽的 FoxP1 依赖性抑制剂，介导 FoxP1 的作用。总之，我们的数据表明转录因子 FoxP1 对于内皮细胞的血管生成功能至关重要，并且作为抑制性指导信号信号蛋白 5B 的抑制剂发挥作用，表明 FoxP1 在新生血管形成的调节中具有重要功能。
Forkhead box (Fox) transcription factors are important regulators of cardiovascular development and several Fox-proteins have recently been shown to modulate embryonic and post-natal angiogenesis. However, the role of the FoxP subfamily, which is highly expressed in cardiovascular tissue, has not been investigated so far. Here, we show that the transcription factor FoxP1 is the highest expressed FoxP-protein in endothelial cells and that it is upregulated at the site of neovascularization during hindlimb ischemia in mice. Silencing of FoxP1 results in a strong inhibition of proliferation, tube formation and migration of cultured endothelial cells. Accordingly, knockdown of FoxP1 in zebrafish was followed by a disruption of intersomitic vascular formation. Using gene expression profiling, we show that FoxP1 induces a specific change of the endothelial transcriptome and functions as a suppressor of semaphorin 5B, which has previously been described as a neuronal inhibitory factor. Our findings now demonstrate that semaphorin 5B also acts as a FoxP1- dependent suppressor of endothelial cell proliferation, migration and sprouting, mediating the effects of FoxP1. In summary, our data indicate that the transcription factor FoxP1 is essential for the angiogenic function of endothelial cells and functions as a suppressor of the inhibitory guidance cue semaphorin 5B, suggesting an important function of FoxP1 in the regulation of neovascularization.
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影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
16.2
作者：
Feiner, L;Koppel, AM;Raper, JA
通讯作者：
Raper, JA
影响因子：
30.5
作者：
Hu, Hui;Wang, Bin;Rao, Anjana
通讯作者：
Rao, Anjana
影响因子：
11.2
作者：
Kessler, O;Shraga-Heled, N;Neufeld, G
通讯作者：
Neufeld, G
DOI：
10.1073/pnas.90.24.11583
发表时间：
1993-12-15
影响因子：
11.1
作者：
LI, C;TUCKER, PW
通讯作者：
TUCKER, PW