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Endothelial Cell Tube Formation Assay for the In Vitro Study of Angiogenesis
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La USP8 endotelial es esencial para la angiogénesis

Alba Pau-Navalón1,2, Tamara González-Costa1,2, María Lancho Lavilla1

  • 1Intercellular Signalling in Cardiovascular Development and Disease Laboratory CNIC, Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.P.S), Madrid, Spain.

Angiogenesis
|January 28, 2026
PubMed
Resumen

La Ubiquitina-Proteasa Específica 8 (USP8) endotelial es vital para la formación de vasos sanguíneos (angiogénesis) durante el desarrollo y después del nacimiento. Su ausencia perjudica el crecimiento vascular, lo que sugiere que la USP8 es un objetivo terapéutico para tratamientos antiangiogénicos.

Palabras clave:
AngiogénesisDesubiquitinantesUSP8VEGFR2Formación de vasos

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Christopher Hughes: An in vitro model for the Study of Angiogenesis Interview
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Christopher Hughes: An in vitro model for the Study of Angiogenesis Interview

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Área de la Ciencia:

  • Biología Celular; Biología del Desarrollo; Biología Molecular

Sus antecedentes:

  • La angiogénesis es fundamental para el desarrollo y las enfermedades, con la señalización del Factor de Crecimiento Endotelial Vascular A (VEGF-A) como regulador clave.; La Ubiquitina-Proteasa Específica 8 (USP8) es una desubiquitinasa que se sabe que influye en el tráfico y la activación de proteínas, incluido el receptor 2 del VEGF (VEGFR2) in vitro.; Comprender el papel de USP8 en las células endoteliales es crucial para desarrollar terapias antiangiogénicas dirigidas.

Objetivo del estudio:

  • Investigar la función in vivo de USP8 en células endoteliales durante diferentes etapas del desarrollo y posnatales.; Dilucidar los mecanismos moleculares por los cuales USP8 regula la angiogénesis.

Principales métodos:

  • Se empleó genética de ratones condicional para eliminar Usp8 en células endoteliales en etapas embrionarias, posnatales tempranas y adultas.; Se evaluaron los fenotipos vasculares, incluida la formación de vasos interesomíticos, la angiogénesis retiniana y la vasculatura cerebral.; Los análisis moleculares se centraron en el tráfico de VEGFR2, la activación del ciclo celular endotelial y las vías de señalización como ERK.

Principales resultados:

  • La deleción específica de Usp8 en endotelios durante la embriogénesis provocó una angiogénesis alterada y letalidad embrionaria.; La deleción posnatal causó defectos graves en la angiogénesis de la retina y el cerebro, mientras que la deleción en adultos no mostró efectos vasculares significativos.; La pérdida de USP8 resultó en la acumulación de VEGFR2 en los endosomas, una reducción de la activación del ciclo celular y la alteración de las vías de señalización.

Conclusiones:

  • La USP8 endotelial es esencial para la angiogénesis durante el desarrollo embrionario y posnatal temprano, pero no para la homeostasis vascular adulta.; USP8 regula la angiogénesis controlando el tráfico de VEGFR2 y la señalización aguas abajo.; USP8 representa un objetivo terapéutico potencial para estrategias antiangiogénicas en enfermedades impulsadas por la formación aberrante de vasos sanguíneos.