Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos.
Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos.
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DOI：
10.3389/fphys.2022.845407
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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血管生成，即新血管从现有血管系统中生长出来，在发育、组织形成和伤口愈合过程中至关重要。响应于血管内皮生长因子（VEGF），内皮细胞被激活以增殖并向信号移动，从而延伸血管。这些事件由VEGF-VEGF受体（Vegfr 2）信号转导指导，而VEGF-VEGF受体信号转导又由硫酸乙酰肝素蛋白聚糖（HSPG）调节。HSPG是共价连接至HS糖胺聚糖链的糖蛋白。跨膜蛋白184 a（Tmem 184 a）最近被鉴定为肝素受体，据信其在体内结合硫酸乙酰肝素链。因此，Tmem 184 a有可能微调VEGF和HS之间的相互作用，调节Vegfr 2依赖性血管生成。Tmem 184 a在斑马鱼尾鳍再生中的功能已被研究，但其在发育血管生成过程中的作用还有待评估。在这里，我们提供了Tmem 184 a如何有助于在斑马鱼胚胎中正确形成脉管系统的见解。首先，我们发现敲低Tmem 184 a会导致斑马鱼胚胎中完整的节间血管（ISV）数量减少。这种表型模拟了vegfr 2b敲除突变体的表型，这些突变体先前已被证明在ISV发育中表现出严重缺陷。然后，我们通过去除Tmem 184 a蛋白内的结合结构域来测试HS相互作用的重要性，该结合结构域对血管生成具有负面影响。发现Tmem 184 a与Vegfr 2b协同作用，表明这两种基因产物在调节血管生成的共同途径中起作用。此外，我们发现Tmem 184 a的敲低导致内皮细胞增殖的增加，但VE-钙粘蛋白的存在量减少。总之，这些发现表明Tmem 184 a是ISV组织成成熟完整血管所必需的。
Angiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vessel. These events are directed by VEGF-VEGF receptor (Vegfr2) signal transduction, which in turn is modulated by heparan sulfate proteoglycans (HSPGs). HSPGs are glycoproteins covalently attached to HS glycosaminoglycan chains. Transmembrane protein 184a (Tmem184a) has been recently identified as a heparin receptor, which is believed to bind heparan sulfate chains in vivo. Therefore, Tmem184a has the potential to fine-tune interactions between VEGF and HS, modulating Vegfr2-dependent angiogenesis. The function of Tmem184a has been investigated in the regenerating zebrafish caudal fin, but its role has yet to be evaluated during developmental angiogenesis. Here we provide insights into how Tmem184a contributes to the proper formation of the vasculature in zebrafish embryos. First, we find that knockdown of Tmem184a causes a reduction in the number of intact intersegmental vessels (ISVs) in the zebrafish embryo. This phenotype mimics that of vegfr2b knockout mutants, which have previously been shown to exhibit severe defects in ISV development. We then test the importance of HS interactions by removing the binding domain within the Tmem184a protein, which has a negative effect on angiogenesis. Tmem184a is found to act synergistically with Vegfr2b, indicating that the two gene products function in a common pathway to modulate angiogenesis. Moreover, we find that knockdown of Tmem184a leads to an increase in endothelial cell proliferation but a decrease in the amount of VE-cadherin present. Together, these findings suggest that Tmem184a is necessary for ISVs to organize into mature, complete vessels.
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影响因子：
2.7
作者：
Blum, Yannick;Belting, Heinz-Georg;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
9.2
作者：
Habeck, H;Odenthal, J;Schulte-Merker, S
通讯作者：
Schulte-Merker, S
影响因子：
16.6
作者：
Corti, Federico;Wang, Yingdi;Simons, Michael
通讯作者：
Simons, Michael
DOI：
10.3390/molecules20046342
发表时间：
2015-04-10
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chiodelli P;Bugatti A;Urbinati C;Rusnati M
通讯作者：
Rusnati M
影响因子：
7.8
作者：
Elfenbein, Arye;Rhodes, John M.;Simons, Michael
通讯作者：
Simons, Michael