VEGFR1 and VEGFR2 involvement in extracellular galectin-1- and galectin-3-induced angiogenesis.
VEGFR1 and VEGFR2 involvement in extracellular galectin-1- and galectin-3-induced angiogenesis.
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DOI：
10.1371/journal.pone.0067029
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Salmon I
中科院分区：
文献类型：
--
作者：
D'Haene N;Sauvage S;Maris C;Adanja I;Le Mercier M;Decaestecker C;Baum L;Salmon I
越来越多的证据表明，细胞外半乳糖凝集素-1和半乳糖凝集素-3促进血管生成。已报道半乳糖凝集素-1和/或半乳糖凝集素-3的表达增加与肿瘤进展相关。因此，确定它们对血管生成的影响至关重要。我们使用两个EC系EA.hy926和HUVEC检测了半乳糖凝集素-1和半乳糖凝集素-3对内皮细胞（EC）生长和管形成的单独和组合作用。通过ELISA和Western印迹法测定血管内皮生长因子受体（VEGFR 1和VEGFR 2）的活化。我们通过邻位连接测定来评估内体中的VEGFR 1和VEGFR 2水平。我们观察到不同的反应，外源半乳糖凝集素取决于EC线。当两种半乳糖凝集素一起添加时，观察到对EA.hy926细胞生长和管形成的增强作用。关注这种增强的作用，我们观察到半乳糖凝集素一起诱导VEGFR 1和VEGFR 2的磷酸化，而半乳糖凝集素-1和-3单独诱导VEGFR 2磷酸化。以相同的方式，加入阻断VEGFR 1抗体完全消除了由两种半乳糖凝集素的组合加入诱导的管形成的增加。相比之下，加入阻断VEGFR 2抗体仅部分抑制该作用。最后，两种半乳糖凝集素的添加诱导VEGFR 1和VEGFR 2内吞池减少，对VEGFR 1内吞池具有显著增强的作用。这些结果表明，半乳糖凝集素-1和半乳糖凝集素-3的联合作用通过VEGFR 1活化对血管生成具有增强的作用，这可能与受体内吞作用的减少有关。
Accumulating evidence suggests that extracellular galectin-1 and galectin-3 promote angiogenesis. Increased expression of galectin-1 and/or galectin-3 has been reported to be associated with tumour progression. Thus, it is critical to identify their influence on angiogenesis. We examined the individual and combined effects of galectin-1 and galectin-3 on endothelial cell (EC) growth and tube formation using two EC lines, EA.hy926 and HUVEC. The activation of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) was determined by ELISA and Western blots. We evaluated the VEGFR1 and VEGFR2 levels in endosomes by proximity ligation assay. We observed different responses to exogenous galectins depending on the EC line. An enhanced effect on EA.hy926 cell growth and tube formation was observed when both galectins were added together. Focusing on this enhanced effect, we observed that together galectins induced the phosphorylation of both VEGFR1 and VEGFR2, whereas galectin-1 and −3 alone induced VEGFR2 phosphorylation only. In the same way, the addition of a blocking VEGFR1 antibody completely abolished the increase in tube formation induced by the combined addition of both galectins. In contrast, the addition of a blocking VEGFR2 antibody only partially inhibited this effect. Finally, the addition of both galectins induced a decrease in the VEGFR1 and VEGFR2 endocytic pools, with a significantly enhanced effect on the VEGFR1 endocytic pool. These results suggest that the combined action of galectin-1 and galectin-3 has an enhanced effect on angiogenesis via VEGFR1 activation, which could be related to a decrease in receptor endocytosis.
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DOI：
10.1177/039463200501800304
发表时间：
2005-07-01
影响因子：
3.5
作者：
D'Haene, N;Maris, C;Salmon, I
通讯作者：
Salmon, I
影响因子：
10.4
作者：
Shtivelband, MI;Juneja, HS;Wu, KK
通讯作者：
Wu, KK
影响因子：
3.7
作者：
Imoukhuede PI;Popel AS
通讯作者：
Popel AS
DOI：
10.1073/pnas.1434429100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Chi, JT;Chang, HY;Brown, PO
通讯作者：
Brown, PO
影响因子：
82.9
作者：
Carmeliet, P;Moons, L;Persico, MG
通讯作者：
Persico, MG