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新型肝素受体跨膜蛋白184a调控成年斑马鱼尾鳍血管生成。

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

作者信息

Farwell Sara Lynn N, Reylander Kimberly G, Iovine M Kathryn, Lowe-Krentz Linda J

机构信息

Department of Biological Sciences, Lehigh UniversityBethlehem, PA, United States.

出版信息

Front Physiol. 2017 Sep 7;8:671. doi: 10.3389/fphys.2017.00671. eCollection 2017.

Abstract

Transmembrane protein 184A (TMEM184A) was recently identified as the heparin receptor in vascular cells. Heparin binds specifically to TMEM184A and induces anti-proliferative signaling . 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 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 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.

摘要

跨膜蛋白184A(TMEM184A)最近被确定为血管细胞中的肝素受体。肝素特异性结合TMEM184A并诱导抗增殖信号。尽管TMEM184A高度保守,但其生理功能仍然未知。本研究的目的是使用成年斑马鱼再生尾鳍作为模型,研究TMEM184A对血管再生的表达和影响。在这里,我们表明Tmem184a在成熟和再生斑马鱼鳍的血管内皮细胞(ECs)中表达。使用两种经过验证的吗啉代寡核苷酸(MO)对Tmem184a进行瞬时吗啉代介导的敲低,会导致再生血管缠结,无法向外生长,并限制正常的整体鳍再生。观察到EC增殖显著增加。与组织培养血管细胞的研究结果一致,肝素具有相反的作用,可降低EC增殖,这也会阻碍整体鳍再生。总的来说,我们的研究表明Tmem184a是血管生成的一种新型调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d6/5594097/92508bca7e99/fphys-08-00671-g0001.jpg

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