BMP-SMAD1/5 Signaling Regulates Retinal Vascular Development
BMP-SMAD1/5 Signaling Regulates Retinal Vascular Development
复制标题
DOI：
10.3390/biom10030488
复制
发表时间：
2020-03-01
期刊：
影响因子：
5.5
通讯作者：
Zwijsen, An
中科院分区：
文献类型：
--
作者：
Benn, Andreas;Alonso, Florian;Zwijsen, An
血管发育是一个经过精心安排的过程，由原有的血管通过萌芽和肠套叠血管生成以及血管重塑形成成熟的血管。骨形态发生蛋白(BMP)通过细胞内Smad1和Smad5效应器调节早期小鼠胚胎萌发的血管生成，但它在其他血管发育过程和其他血管床中的作用尚不完全清楚。在这里，我们通过可诱导的内皮特异性的Smad1和Smad5的缺失来研究Smad1/5在出生后早期视网膜血管发育中的功能。我们观察到动脉-静脉畸形的形成是在血流量高的区域，而在血管生成前沿，功能性的尖端细胞越来越少。血管丛区域明显高密度，这与减少血管退缩和异常的血管环形成有关。综上所述，我们的结果强调了Smad1/5在出生后早期视网膜血管形成和重塑中的重要功能。
Vascular development is an orchestrated process of vessel formation from pre-existing vessels via sprouting and intussusceptive angiogenesis as well as vascular remodeling to generate the mature vasculature. Bone morphogenetic protein (BMP) signaling via intracellular SMAD1 and SMAD5 effectors regulates sprouting angiogenesis in the early mouse embryo, but its role in other processes of vascular development and in other vascular beds remains incompletely understood. Here, we investigate the function of SMAD1/5 during early postnatal retinal vascular development using inducible, endothelium-specific deletion of Smad1 and Smad5. We observe the formation of arterial-venous malformations in areas with high blood flow, and fewer and less functional tip cells at the angiogenic front. The vascular plexus region is remarkably hyperdense and this is associated with reduced vessel regression and aberrant vascular loop formation. Taken together, our results highlight important functions of SMAD1/5 during vessel formation and remodeling in the early postnatal retina.