Novel Heparin Receptor Transmembrane Protein 184a Regulates Angiogenesis in the Adult Zebrafish Caudal Fin.

Novel Heparin Receptor Transmembrane Protein 184a Regulates Angiogenesis in the Adult Zebrafish Caudal Fin.
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DOI:
10.3389/fphys.2017.00671
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发表时间:
2017
影响因子:
4
通讯作者:
Lowe-Krentz LJ
Lowe-Krentz LJ
中科院分区:
医学2区
文献类型:
--
作者:
Farwell SLN;Reylander KG;Iovine MK;Lowe-Krentz LJ

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跨膜蛋白184A(TMEM184A)是新近发现的血管细胞中的肝素受体。肝素能与TMEM184A特异性结合,在体外诱导抗增殖信号。尽管TMEM184A高度保守,但其生理功能尚不清楚。本研究以成年斑马鱼再生尾鳍为模型,研究TMEM184A在体内的表达及其对血管再生的影响。在这里,我们发现Tem184a在成熟和再生的斑马鱼鳍的血管内皮细胞(ECs)中表达。使用两种有效的吗啡(MO)对Tem184a进行瞬时吗啡(MO)介导的敲除会导致缠绕的再生血管不向外生长,并限制正常的整体鳍再生。观察到EC的增殖显著增加。与组织培养血管细胞的体外工作一致,肝素具有相反的作用,它减少了EC的增殖,这也阻碍了整个鳍的再生。综上所述,我们的研究表明Tem184a是一种新的血管生成调节因子。
Transmembrane protein 184A (TMEM184A) was recently identified as the heparin receptor in vascular cells. Heparin binds specifically to TMEM184A and induces anti-proliferative signaling in vitro. Though it is highly conserved, the physiological function of TMEM184A remains unknown. The objective of this study was to investigate the expression and effects on vascular regeneration of TMEM184A using the adult zebrafish regenerating caudal fin as an in vivo model. Here, we show that Tmem184a is expressed in vascular endothelial cells (ECs) of mature and regenerating zebrafish fins. Transient morpholino (MO)-mediated knockdown of Tmem184a using two validated MOs results in tangled regenerating vessels that do not grow outward and limit normal overall fin regeneration. A significant increase in EC proliferation is observed. Consistent with in vitro work with tissue culture vascular cells, heparin has the opposite effect and decreases EC proliferation which also hinders overall fin regeneration. Collectively, our study suggests that Tmem184a is a novel regulator of angiogenesis.
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