2024-03-28T22:54:45Zhttp://buleria.unileon.es/oai/requestoai:buleria.unileon.es:10612/151562022-11-04T13:01:22Zcom_10612_17col_10612_18
Maeso Alonso, Laura
Alonso-Olivares, Hugo
Martínez-García, Nicole
López-Ferreras, Lorena
Villoch-Fernández, Javier
Puente-Santamaría, Laura
Colas-Algora, Natalia
Fernández-Corona, Alfonso
Lorenzo-Marcos, María Elena
Jiménez, Benilde
Holmgren, Lars
Wilhelm, Margareta
Millan, Jaime
del Peso, Luis
Claesson-Welsh, Lena
Marqués Martínez, Margarita
Marín Vieira, María Carmen
2022-10-04T10:22:40Z
2022-10-04T10:22:40Z
Maeso-Alonso, L., Alonso-Olivares, H., Martínez-García, N. et al. p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin. Cell. Mol. Life Sci. 79, 535 (2022). https://doi.org/10.1007/s00018-022-04560-3
1420-682X
https://link.springer.com/article/10.1007/s00018-022-04560-3
http://hdl.handle.net/10612/15156
10.1007/s00018-022-04560-3
1420-9071
[EN] Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell–cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Atribución 4.0 Internacional
Biología
p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin
info:eu-repo/semantics/article