Cdc42 has important roles in postnatal angiogenesis and vasculature formation
Cdc42 has important roles in postnatal angiogenesis and vasculature formation
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Cdc42 在出生后血管生成和脉管系统形成中具有重要作用
DOI：
10.1016/j.ydbio.2021.05.002
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发表时间：
2021
影响因子：
2.7
通讯作者：
Iijima Takehiko
中科院分区：
文献类型：
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作者：
Yoshida Yuko;Yamada Atsushi;Akimoto Yoshihiro;Abe Kyoko;Matsubara Sachie;Hayakawa Junri;Tanaka Junichi;Kinoshita Mitsuhiro;Kato Tadashi;Ogata Hiroaki;Sakashita Akiko;Mishima Kenji;Kubota Yoshiaki;Kawakami Hayato;Kamijo Ryutaro;Iijima Takehiko
Cdc42是Rho家族低分子量G蛋白，在细胞骨架重排、细胞粘附、细胞增殖分化等多种细胞功能中发挥重要作用。为了研究Cdc42在血管内皮细胞活动中的作用，我们制造了Cdc42条件敲除小鼠，其中Cdc42在血管内皮细胞中时间特异性缺失（Cdc42 fl/fl; VE-Cad CreERT: Cdc42 cKO）。当Cdc42基因在出生后被删除时，Cdc42 cKO小鼠比对照小鼠更小，并在出生后第8天（P8）至P10天死亡。尸检结果证实，这些小鼠在大多数器官的血管中都有各种病理异常，如血流阻塞和血细胞入侵。电镜观察还发现毛细血管内皮细胞脱离基底膜，巨噬细胞诱导内皮细胞吞噬死亡。此外，由于内皮细胞增殖缺陷，来自Cdc42 cKO小鼠的样本中VEGF-A诱导的主动脉环血管发芽减少。这些结果表明，血管内皮细胞中的Cdc42在出生后血管形成中起重要作用。
Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 fl/fl; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Necropsy findings confirmed that these mice had various pathological aberrances in the vessels of most organs, such as blood flow congestion and blood cell invasion. Electron microscopic observations also revealed that capillary endothelial cells were detached from the basement membrane as well as phagocytosis of dead endothelial cells induced by macrophages. Moreover, vascular sprouting from aortic rings induced by VEGF-A was diminished in samples from the Cdc42 cKO mice because of an endothelial cell proliferation defect. These results suggest that Cdc42 in vascular endothelial cells has important roles in blood vessel formation after birth.