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The vascular endothelial growth factor (VEGF) and its high-affinity binding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature. Here we report that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation. Mouse embryos(More)
Polycythemia is often associated with erythropoietin (EPO) overexpression and defective oxygen sensing. In normal cells, intracellular oxygen concentrations are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins, which tag hypoxia-inducible factor (HIF) alpha subunits for polyubiquitination and proteasomal degradation by oxygen-dependent(More)
BACKGROUND Prolyl hydroxylase domain (PHD) proteins, including PHD1, PHD2, and PHD3, mediate oxygen-dependent degradation of hypoxia-inducible factor (HIF)-alpha subunits. Although angiogenic roles of hypoxia-inducible factors are well known, the roles of PHDs in the vascular system remain to be established. METHODS AND RESULTS We evaluated angiogenic(More)
Erythropoiesis must be tightly balanced to guarantee adequate oxygen delivery to all tissues in the body. This process relies predominantly on the hormone erythropoietin (EPO) and its transcription factor hypoxia inducible factor (HIF). Accumulating evidence suggests that oxygen-sensitive prolyl hydroxylases (PHDs) are important regulators of this entire(More)
Angiogenesis is an important component in the development of thyroid goitre. Vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens involved in normal angiogenesis and in tumour development. The purpose of this study was to determine the distribution of VEGF in thyroid tissues during goitre formation, and to(More)
PURPOSE To investigate the mechanisms governing corneal neovascularization and the appearance of goblet cells in a murine model of limbal insufficiency. METHODS The spatial and time-dependent relationship between corneal neovascularization and goblet cell density was analyzed in corneal flatmounts. Immunohistochemical detection of the vascular endothelial(More)
Prolyl hydroxylase domain 2 protein (PHD2) signals the degradation of hypoxia-inducible factor (HIF)-1alpha by hydroxylating specific prolyl residues located within oxygen-dependent degradation domains. As expected, endothelial cells (ECs) overexpressing PHD2 had reduced HIF-1alpha and vascular endothelial growth factor-A expression and failed to accelerate(More)
Background—The development of the vascular system is a complex process that involves communications among multiple cell types. As such, it is important to understand whether a specific gene regulates vascular development directly from within the vascular system or indirectly from nonvascular cells. Hypoxia-inducible factor-2␣ (Hif-2␣, or endothelial PAS(More)
Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2). Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF. Recently, specific ligands for VEGFR-1 have been reported to have beneficial effects when used to treat ischemic diseases. However, the role of(More)
Mesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of(More)