血管新生における力の機能についての研究

力在血管生成中的作用研究

• 批准号: 15F14385
• 负责人: 望月 直樹
• 金额: $ 1.41万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2015
• 资助国家: 日本
• 起止时间: 2015-04-24 至 2018-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15F14385/
• 关键词: angiogenesis; endothelial cell; actin; Marcks1; zebrafish; 血管新生; 細胞骨格; ミオシン; アクチン

I identified Marcksl1, an actin-binding protein, as a molecular regulator of endothelial cell cortex during blood vessel morphogenesis in the zebrafish embryo. During lumen formation, Marcksl1 localization is enriched in the apical membrane. Overexpression of the protein perturbed cell cortex integrity so that 1) excessive blebs form at the apical membrane during lumen expansion and 2) ectopic blebs from at the basal membrane in perfused vessels that dissipate after inhibiting blood flow. In addition, endothelial cells with increased Marcksl1 expression are irregular in shape so that they are more dilated than wild type cells. These findings suggest that Marcksl1 regulates endothelial cell cortex dynamics and strength and that a robust cortex is required to resist haemodynamic forces and maintain blood vessel structure.

我发现 Marcksl1（一种肌动蛋白结合蛋白）是斑马鱼胚胎血管形态发生过程中内皮细胞皮层的分子调节剂。在管腔形成过程中，Marcksl1 定位在顶膜中丰富。该蛋白质的过度表达扰乱了细胞皮层的完整性，从而导致 1) 管腔扩张期间在顶膜处形成过多的气泡，2) 灌注血管中基底膜处的异位气泡在抑制血流后消散。此外，Marcksl1 表达增加的内皮细胞形状不规则，因此它们比野生型细胞更扩张。这些发现表明 Marcksl1 调节内皮细胞皮层动力学和强度，并且需要坚固的皮层来抵抗血流动力学力和维持血管结构。

项目成果

Max-Delbruck Center(Germany)

马克斯-德尔布鲁克中心（德国）

Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo.

体内血管生成过程中，血流通过反膜起泡驱动管腔形成。

• DOI: 10.1038/ncb3320
• 发表时间: 2016
• 作者: Gebala V; Collins R; Geudens I; Phng LK; Gerhardt H
• 通讯作者: Gerhardt H

Dynamic endothelial cell rearrangements drive developmental vessel regression.

动态内皮细胞重排驱动发育血管退化。

• DOI: 10.1371/journal.pbio.1002125
• 发表时间: 2015
• 作者: Franco CA; Jones ML; Bernabeu MO; Geudens I; Mathivet T; Rosa A; Lopes FM; Lima AP; Ragab A; Collins RT; Phng LK; Coveney PV; Gerhardt H.
• 通讯作者: Gerhardt H.

Formin-mediated actin polymerization at endothelial junctions is required for vessel lumen formation and stabilization.

内皮连接处福尔明介导的肌动蛋白聚合是血管腔形成和稳定所必需的。

• DOI: 10.1016/j.devcel.2014.11.017
• 发表时间: 2015
• 作者: Phng LK; Gebala V; Bentley K; Philippides A; Wacker A; Mathivet T; Sauteur L; Stanchi F; Belting HG; Affolter M; Gerhardt H.
• 通讯作者: Gerhardt H.

Actin dynamics in lumen formation during sprouting angiogenesis

发芽血管生成过程中管腔形成的肌动蛋白动力学

• 发表时间: 2016
• 作者: Li