Tip-cell behavior is regulated by transcription factor FoxO1 under hypoxic conditions in developing mouse retinas.
Angiogenesis
; 21(2): 203-214, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29185141
ABSTRACT
Forkhead box protein O1 (FoxO1) is a transcription factor and a critical regulator of angiogenesis. Various environmental stimuli, including growth factors, nutrients, shear stress, oxidative stress and hypoxia, affect FoxO1 subcellular localization and strongly influence its transcriptional activity; however, FoxO1-localization patterns in endothelial cells (ECs) during development have not been clarified in vivo. Here, we reported that FoxO1 expression was observed in three layers of angiogenic vessels in developing mouse retinas and that among these layers, the front layer showed high levels of FoxO1 expression in the nuclei of most tip ECs. Because tip ECs migrate toward the avascular hypoxic area, we focused on hypoxia as a major stimulus regulating FoxO1 subcellular localization in tip cells. In cultured ECs, FoxO1 accumulated into the nucleus under hypoxic conditions, with hypoxia also inducing expression of tip-cell-specific genes, including endothelial-specific molecule 1 (ESM1), which was suppressed by FoxO1 knockdown. Additionally, in murine models, EC-specific FoxO1 deletion resulted in reduced ESM1 expression and suppressed tip-cell migration during angiogenesis. These findings indicated roles for FoxO1 in tip-cell migration and that its transcriptional activity is regulated by hypoxia.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retina
/
Neovascularización Retiniana
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Regulación de la Expresión Génica
/
Células Endoteliales
/
Proteína Forkhead Box O1
/
Hipoxia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Angiogenesis
Asunto de la revista:
HEMATOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón