EGFL7 regulates sprouting angiogenesis and endothelial integrity in a human blood vessel model
EGFL7 regulates sprouting angiogenesis and endothelial integrity in a human blood vessel model
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DOI：
10.1016/j.biomaterials.2019.01.022
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发表时间：
2019-03-01
期刊：
影响因子：
14
通讯作者：
Matsunaga, Yukiko T.
中科院分区：
文献类型：
--
作者：
Usuba, Ryo;Pauty, Joris;Matsunaga, Yukiko T.
阐明发芽血管生成和通透性的机制将有助于开发更有效的治疗各种疾病的方法，包括视网膜病变、癌症和其他血管疾病。我们重点研究了表皮生长因子样结构域7 (EGFL7)，它在NOTCH信号传导和血管新生芽的组织中起重要作用。我们建立了体外微血管模型，并在组织水平上研究了EGFL7的作用。我们发现EGFL7敲低抑制vegf - a诱导的新生血管生成，并伴有内皮丝状伪足的过度生成和内皮细胞基侧胶原IV沉积的减少。我们还观察到屏障功能受损，这反映了炎症状况。此外，我们的研究结果表明，粘附连接的正常形成和VE-cadherin的磷酸化受到干扰。总之，通过使用3D微血管模型，我们确定了EGFL7在发芽血管生成过程中内皮功能中的新作用。
Elucidating the mechanisms underlying sprouting angiogenesis and permeability should enable the development of more effective therapies for various diseases, including retinopathy, cancer, and other vascular disorders. We focused on epidermal growth factor-like domain 7 (EGFL7) which plays an important role in NOTCH signaling and in the organization of angiogenic sprouts. We developed an EGFL7-knockdown in vitro microvessel model and investigated the effect of EGFL7 at a tissue level. We found EGFL7 knockdown suppressed VEGF-A-induced sprouting angiogenesis accompanied by an overproduction of endothelial filopodia and reduced collagen IV deposition at the basal side of endothelial cells. We also observed impaired barrier function which reflected an inflammatory condition. Furthermore, our results showed that proper formation of adherens junctions and phosphorylation of VE-cadherin was disturbed. In conclusion, by using a 3D microvessel model we identified novel roles for EGFL7 in endothelial function during sprouting angiogenesis.