Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability.
Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability.
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DOI：
10.1371/journal.pone.0018076
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发表时间：
2011-03-25
期刊：
影响因子：
3.7
通讯作者：
Boulton ME
中科院分区：
文献类型：
--
作者：
Cai J;Wu L;Qi X;Shaw L;Li Calzi S;Caballero S;Jiang WG;Vinores SA;Antonetti D;Ahmed A;Grant MB;Boulton ME
血管通透性增加是组织缺血和血管生成的早期特征。虽然VEGF家族成员是内皮通透性的有效促进剂，但胎盘生长因子（PlGF）的作用仍存在激烈争论。在这里，我们研究了PlGF亚型1和2，并在体外和体内的证据表明，PlGF-1，但不是PlGF-2，可以抑制VEGF诱导的渗透性，但只有在一个关键的窗口后VEGF暴露。PlGF-1通过反式激活Sp1和Sp3与VE-钙粘蛋白启动子的相互作用促进VE-钙粘蛋白表达，随后稳定跨内皮连接，但仅在VEGF激活内皮细胞后。PlGF-1调节与VE-钙粘蛋白向质膜的快速定位和酪氨酸残基的去磷酸化相关的血管通透性，所述酪氨酸残基的去磷酸化先于在密蛋白5酪氨酸磷酸化和膜定位中观察到的变化。在此期间，PLGF-1对VEGF诱导的渗透性发挥其作用的关键窗口突出了这项工作的翻译意义的重要性，因为PLGF-1可能充当内源性抗渗透性因子，其有效性限于血管损伤后的精确时间点。因此，将模仿自然方法的临床方法将把治疗限制在损伤后的精确时间间隔，并只在治疗窗口期间使用药剂。
Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.
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影响因子：
4.8
作者：
Cai, J;Jiang, WG;Boulton, M
通讯作者：
Boulton, M
影响因子：
3.1
作者：
Cai, J;Jiang, WG;Boulton, M
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Boulton, M
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82.9
作者：
Carmeliet, P;Moons, L;Persico, MG
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Persico, MG
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82.9
作者：
Autiero, M;Waltenberger, J;Carmeliet, P
通讯作者：
Carmeliet, P
影响因子：
20.1
作者：
Björndahl, M;Cao, RH;Cao, YH
通讯作者：
Cao, YH