Unravelling the role of aquaporins in blood vessel development

揭示水通道蛋白在血管发育中的作用

• 批准号: 22K06244
• 负责人: Kondrychyn Igor
• 金额: $ 2.58万
• 依托单位: Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K06244/
• 关键词: blood vessel development; aquaporins; zebrafish

1. Knockout of aqp1a.1, aqp8a.1 or both genes results in incomplete formation of intersegmental vessels (ISVs) in the zebrafish trunk. This phenotype is due to a defective sprouting angiogenesis in aquaporin mutants.2. During sprouting angiogenesis aqp1a.1 but not aqp8a.1 is expressed in the dorsal aorta, and aqp1a.1 expression is enriched in tip cells and in endothelial cells (ECs) that would be protrude from the dorsal aorta.3. In the absence of aqp1a.1 and aqp8a.1 there is a delay in endothelial tip cell protrusion from the dorsal aorta and a decrease in tip cell velocity during ISV formation. Also, the loss of both Aqp1a.1 and Aqp8a.1 led to a decrease in the number of the formed filopodia as well as a decrease in filopodia length. In the absence of filopodia, wild type ECs are still able to migrate to form ISVs, while ECs in aquaporin mutants are not, suggesting that both filopodia-mediated migration and aquaporins may function synergistically to promote EC migration during sprouting angiogenesis.4. We also found that the loss of aqp1a.1 but not aqp8a.1 results in a decrease of hematopoietic stem and progenitor cells (HSPCs) formation. In the zebrafish, HSPCs are generated through the budding of hemogenic ECs from the ventral floor of the dorsal aorta.

1.敲除aqp1a.1、aqp8a.1或两个基因都会导致斑马鱼躯干中节间血管（ISV）的不完全形成。这种表型是由于水通道蛋白突变体中有缺陷的出芽血管生成。在出芽过程中，aqp1a.1在背侧主动脉中表达，而aqp8a.1不表达，aqp1a.1的表达在尖端细胞和从背侧主动脉突出的内皮细胞（EC）中富集.在缺乏aqp1a.1和aqp8a.1的情况下，在ISV形成期间，内皮尖端细胞从背主动脉突出延迟并且尖端细胞速度降低。此外，Aqp1a.1和Aqp8a.1的缺失导致所形成的丝状伪足的数量减少以及丝状伪足长度减少。在丝状伪足缺失的情况下，野生型内皮细胞仍然能够迁移形成ISV，而水通道蛋白突变体中的内皮细胞则不能，这表明丝状伪足介导的迁移和水通道蛋白可能协同作用，在出芽血管生成过程中促进内皮细胞迁移.我们还发现aqp1a.1的缺失而不是aqp8a.1的缺失导致造血干细胞和祖细胞（HSPCs）形成的减少。在斑马鱼中，HSPC是通过从背主动脉的腹侧底出芽的生血EC产生的。

项目成果

Distinct roles of aquaporins in blood vessel formation

水通道蛋白在血管形成中的独特作用

• 发表时间: 2022
• 作者: 日下部りえ;倉谷滋;八杉徹雄;Igor Kondrychyn
• 通讯作者: Igor Kondrychyn