ANKFY1 is essential for retinal endothelial cell proliferation and migration via VEGFR2/Akt/eNOS pathway
ANKFY1 is essential for retinal endothelial cell proliferation and migration via VEGFR2/Akt/eNOS pathway
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DOI：
10.1016/j.bbrc.2020.10.032
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Tanaka, Miruto;Nakamura, Shinsuke;Hara, Hideaki
内皮细胞增殖和迁移的失调是血管生成疾病的标志。其中，眼部血管生成过多是导致失明的主要原因。血管内皮生长因子(VEGF)-VEGF受体2 （VEGFR2）信号在血管生成、内皮细胞增殖和迁移中起着至关重要的作用。在这里，我们发现锚蛋白重复和含有1的FYVE结构域（ANKFY1）是一种rab5 - gtp相互作用的蛋白，是视网膜内皮细胞增殖和迁移所必需的。在VEGF存在或不存在的情况下，ANKFY1敲低显著抑制人视网膜微血管内皮细胞（HRMECs）的细胞生长。ANKFY1的缺失也抑制了HRMEC的迁移。Western blot分析显示，ANKFY1敲低可降低细胞表面VEGFR2水平。相比之下，qRT-PCR分析显示，ANKFY1敲低对VEGFR2 mRNA水平没有影响。我们还发现ANKFY1敲低的hrmes中蛋白激酶B/内皮型一氧化氮合酶（Akt/eNOS）通路的衰减。总之，我们的研究结果揭示了ANKFY1在视网膜内皮细胞生长和迁移中的新功能。(C) 2020爱思唯尔公司版权所有。
Dysregulation of endothelial cell proliferation and migration are hallmarks of angiogenic diseases. Among them, excessive ocular angiogenesis is a major cause of blindness. Vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling plays crucial roles in angiogenesis, endothelial cell proliferation and migration. Here, we showed that ankyrin repeat and FYVE domain containing 1 (ANKFY1), a Rab5-GTP-interacting protein, is required for retinal endothelial cell proliferation and migration. ANKFY1 knockdown significantly suppressed cell growth of human retinal microvascular endothelial cells (HRMECs) in the presence or absence of VEGF. HRMEC migration was also inhibited by depletion of ANKFY1. Western blot analysis showed that ANKFY1 knockdown reduced cell surface VEGFR2 level. In contrast, qRT-PCR analysis indicated that ANKFY1 knockdown had no effect on VEGFR2 mRNA levels. We also found that the attenuation of the protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) pathway in ANKFY1 knockdown HRMECs. In conclusion, our findings revealed novel functions of ANKFY1 in cell growth and migration of retinal endothelial cells. (C) 2020 Elsevier Inc. All rights reserved.