VEGF and FGF prime vascular tube morphogenesis and sprouting directed by hematopoietic stem cell cytokines.
Blood
; 117(14): 3709-19, 2011 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-21239704
ABSTRACT
Here, we demonstrate a novel, direct-acting, and synergistic role for 3 hematopoietic stem cell cytokines stem cell factor, interleukin-3, and stromal derived factor-1α, in controlling human endothelial cell (EC) tube morphogenesis, sprouting, and pericyte-induced tube maturation under defined serum-free conditions in 3-dimensional matrices. Angiogenic cytokines such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) alone or VEGF/FGF combinations do not support these responses. In contrast, VEGF and FGF prime EC responses to hematopoietic cytokines via up-regulation of c-Kit, IL-3Rα, and C-X-C chemokine receptor type 4 from either human ECs or embryonic quail vessel explants. In support of these findings, EC Runx1 is demonstrated to be critical in coordinating vascular morphogenic responses by controlling hematopoietic cytokine receptor expression. Combined blockade of hematopoietic cytokines or their receptors in vivo leads to blockade of developmental vascularization in quail embryos manifested by vascular hemorrhage and disrupted vascular remodeling events in multiple tissue beds. This work demonstrates a unique role for hematopoietic stem cell cytokines in vascular tube morphogenesis and sprouting and further demonstrates a novel upstream priming role for VEGF and FGF to facilitate the action of promorphogenic hematopoietic cytokines.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pseudópodes
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Capilares
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Células-Tronco Hematopoéticas
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Endotélio Vascular
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Citocinas
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Neovascularização Fisiológica
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Fator A de Crescimento do Endotélio Vascular
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Fatores de Crescimento de Fibroblastos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article