Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth.

Abstract

Vascular end lgwt factor (VEGF) b a polyetide mitogen that mulats the growth of endotlil clsin vigro and promotesthe growth ofblood vess in vivo. We have recetly shown that the ths-like receptor tyrosne kinae (flt) Is a receptor for VEGF. Here we used in siu hybrdzation to show that, In adult mouse tissues, the pattern offltexp-esslon was consstent with lo t io n endothe . We also show thatfkwas expsed endothellum during neovacularizton of heai skin wounds and during eady vascular devdopment In mose embyos. Moreover,ft was expsed In populatons of embyoniccels from which endotellIum Is derived such as early yolk sac mesenchyme. The epreson offt In the endotelium of both developing and mature blood vessels that VEGF might rgulate endothelal dierentition, blod vessel growth, and vasular repair.

Coordinate expression of vascular endothelial growth factor receptor‐1 (fit‐1) and its ligand suggests a paracrine regulation of murine vascular development

“…This hypothesis is further substantiated by the observation that both VEGF receptors were expressed in the growing vasculature of the decidua (this study and Millauer et al, 1993) and by the presence of high affinity binding sites in blood vessels of the maternal decidua (Jakeman et al, 1993). Peters et al (1993) reported VEGFRlAlt-1 expression by in situ hybridization during the period from E9.5 to E12.5 when major vascular structures such as the heart and the dorsal aorta have already formed. Our results extend these observations and show that VEGFRl/flt-1 is already expressed during the emergence of the first endothelial cells and that most blood vessels and capillaries in the embryo co-expressed both VEGF receptors throughout vascular development.…”

A flk‐1 promoter/enhancer reporter transgenic Xenopus laevis generated using the Sleeping Beauty transposon system: An in vivo model for vascular studies

“…Several reports demonstrate that flk-1 is expressed in bipotential progenitor cells that can give rise to vascular endothelial cells and blood cells (Millauer et al, 1993;Peters et al, 1993;Yamaguchi et al, 1993;Huber et al, 2004). The presence of circulating GFP-positive cells in the transgenic tadpoles may reflect the maintenance of GFP protein in cells derived from these progenitors.…”

“…The receptor tyrosine kinase flk-1/ vegfr2/KDR-1 is expressed in the developing embryonic vasculature as well as bipotential hemangioblasts, cells that become either blood or endothelial cells (Millauer et al, 1993;Peters et al, 1993;Yamaguchi et al, 1993;Huber et al, 2004). Targeted deletion of flk-1 results in the failure of the vascular system to develop in mice, demonstrating an essential role for this receptor tyrosine kinase in this process (Shalaby et al, 1995).…”

A peptide corresponding to the neuropilin-1-binding site on VEGF165 induces apoptosis of neuropilin-1-expressing breast tumour cells

“…Having demonstrated that murine 4T1 and human MDA-MB-231 tumour cells express NP-1 and endothelial cells (HU-VEC's) express both NP-1 and KDR, we studied the effect of anti-NP1 and anti-KDR peptides on apoptosis. HUVECs were used as a positive control as these are known to express Flt-1, KDR and NP-1 (Peters et al, 1993 Figure 3A, B and C, respectively). Anti-KDR peptide induced significant apoptosis of HUVECs relative to controls (14177% vs control, Po0.05) but had no effect on tumour cell apoptosis in murine and human tumour cells (4T1, 77.12720.82%; MDA-MB-231, 86.2475.61% vs control), consistent with the lack of expression of Flk-1/KDR in these cells.…”