SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis.
SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis.
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SARAF和Orai1有助于内皮细胞活化和血管生成。
DOI：
10.3389/fcell.2021.639952
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发表时间：
2021
影响因子：
5.5
通讯作者：
Smani T
中科院分区：
文献类型：
--
作者：
Galeano-Otero I;Del Toro R;Khatib AM;Rosado JA;Ordóñez-Fernández A;Smani T
血管生成是一个多步骤的过程，控制内皮细胞（EC）从预先存在的血管床形成新的血管。这一过程受到促血管生成因子（如血管内皮生长因子（VEGF））的严格调控，其促进涉及细胞内Ca2+浓度（[Ca2 +] i）增加的信号传导途径。最近的证据表明，钙池操作的钙进入（SOCE）可能在血管生成中发挥作用。然而，关于SARAF（SOCE相关调节因子）和Orai 1（钙库操纵的钙通道（SOCC）的成孔亚基）在血管生成中的作用知之甚少。在这里，我们表明GSK-7975A的SOCE抑制作用阻断了主动脉出芽，以及人脐静脉内皮细胞（HUVEC）管的形成和迁移。腹膜内注射GSK-7975A还延迟了在出生后第6天在小鼠中评估的视网膜血管系统的发育，因为它减少了血管长度和连接点的数量，同时增加了腔隙性。此外，我们发现SARAF和Orai1参与VEGF介导的[Ca2 +] i增加，并且使用siRNA敲低它们会损害HUVEC管形成、增殖和迁移。最后，免疫染色和原位邻近连接试验表明，SARAF可能与Orai1在HUVEC中相互作用。因此，这些发现首次显示了SARAF和Orai1在EC中的功能性相互作用，并强调了它们在血管生成过程的不同步骤中的重要作用。
Angiogenesis is a multistep process that controls endothelial cells (ECs) functioning to form new blood vessels from preexisting vascular beds. This process is tightly regulated by pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which promote signaling pathways involving the increase in the intracellular Ca2+ concentration ([Ca2+]i). Recent evidence suggests that store-operated calcium entry (SOCE) might play a role in angiogenesis. However, little is known regarding the role of SARAF, SOCE-associated regulatory factor, and Orai1, the pore-forming subunit of the store-operated calcium channel (SOCC), in angiogenesis. Here, we show that SOCE inhibition with GSK-7975A blocks aorta sprouting, as well as human umbilical vein endothelial cell (HUVEC) tube formation and migration. The intraperitoneal injection of GSK-7975A also delays the development of retinal vasculature assessed at postnatal day 6 in mice, since it reduces vessel length and the number of junctions, while it increases lacunarity. Moreover, we find that SARAF and Orai1 are involved in VEGF-mediated [Ca2+]i increase, and their knockdown using siRNA impairs HUVEC tube formation, proliferation, and migration. Finally, immunostaining and in situ proximity ligation assays indicate that SARAF likely interacts with Orai1 in HUVECs. Therefore, these findings show for the first time a functional interaction between SARAF and Orai1 in ECs and highlight their essential role in different steps of the angiogenesis process.
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DOI：
10.1111/j.1549-8719.2010.00075.x
发表时间：
2011-02
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Gould DJ;Vadakkan TJ;Poché RA;Dickinson ME
通讯作者：
Dickinson ME
影响因子：
5.3
作者：
Logsdon EA;Finley SD;Popel AS;Mac Gabhann F
通讯作者：
Mac Gabhann F
影响因子：
4.6
作者：
Albarran L;Lopez JJ;Amor NB;Martin-Cano FE;Berna-Erro A;Smani T;Salido GM;Rosado JA
通讯作者：
Rosado JA
影响因子：
4.8
作者：
Antigny, Fabrice;Girardin, Nathalie;Frieden, Maud
通讯作者：
Frieden, Maud
影响因子：
2.8
作者：
Munaron, Luca;Tomatis, Cristiana;Pla, Alessandra Fiorio
通讯作者：
Pla, Alessandra Fiorio