RT Journal Article
T1 SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis.
A1 Galeano-Otero, Isabel
A1 Del-Toro, Raquel
A1 Khatib, Abdel-Majid
A1 Rosado, Juan Antonio
A1 Ordoñez-Fernandez, Antonio
A1 Smani, Tarik
K1 HUVEC
K1 Orai1
K1 SARAF
K1 SOCE
K1 angiogenesis
AB 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.
PB Frontiers Research Foundation
SN 2296-634X
YR 2021
FD 2021-03-04
LK http://hdl.handle.net/10668/17379
UL http://hdl.handle.net/10668/17379
LA en
NO Galeano-Otero I, Del Toro R, Khatib AM, Rosado JA, Ordóñez-Fernández A, Smani T. SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis. Front Cell Dev Biol. 2021 Mar 4;9:639952.
DS RISalud
RD Jul 30, 2025