The Mouse Gene for Vascular Endothelial Growth Factor

Shima, David T.; Kuroki, Masahide; Deutsch, Urban; Ng, Y. Jack; Adamis, Anthony P.; D’Amore, Patricia A.

doi:10.1074/jbc.271.7.3877

Cited by 272 publications

(107 citation statements)

References 42 publications

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“…As for the VEGF gene (22), the VEGF-C gene promoter lacks consensus TATA and CCAAT sequences. Instead, it has putative binding sites for Sp-1, a ubiquitous nuclear protein that can initiate transcription from TATA-less genes (39) and a long GC-rich 5Ј-untranslated region, which is typical for several growth factor genes and is postulated to have a role in translational regulation (22,23,28,40). In addition, sequences upstream of the VEGF-C translation start site were found to contain consensus binding sites for the AP-2 transcription factor.…”

Section: Identification Of the Vegf-c Promoter Region And The Mrna Startmentioning

confidence: 99%

“…Lambda inserts varying from 10 to 15 kb in size were subcloned into pBluescript SKϩ (Stratagene, La Jolla, CA). Computer analysis of the promoter region was performed with the MatInspector program (23).…”

Section: Isolation Of Human and Mouse Genomicmentioning

confidence: 99%

“…This promoter is TATAless and responds to various effectors, including hypoxia, tumor necrosis factor-␣, and basic fibroblast growth factor (24). A 1.2-kb 5Ј-flanking region of the mouse VEGF gene contains basal promoter activity (21,23). However, although the promoter also has a hypoxia-regulated element, VEGF gene induction by hypoxia is also effected via mRNA stabilization (25).…”

mentioning

confidence: 99%

“…The isolation and characterization of the VEGF gene promoter has been reported from human, rat, and mouse species (21)(22)(23). The human promoter was shown to contain multiple binding sites for Sp-1, AP-1, and AP-2 transcription factors and hypoxia-regulated elements (21)(22)(23).…”

mentioning

confidence: 99%

“…The human promoter was shown to contain multiple binding sites for Sp-1, AP-1, and AP-2 transcription factors and hypoxia-regulated elements (21)(22)(23). This promoter is TATAless and responds to various effectors, including hypoxia, tumor necrosis factor-␣, and basic fibroblast growth factor (24).…”

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confidence: 99%

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Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

Chilov¹,

Kukk²,

Taira

et al. 1997

Journal of Biological Chemistry

173

110

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We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C 6 C 10 CRC, and exon 6 encodes additional C 10 CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-B transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.

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Section: Identification Of the Vegf-c Promoter Region And The Mrna Startmentioning

confidence: 99%

Section: Isolation Of Human and Mouse Genomicmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

Chilov¹,

Kukk²,

Taira

et al. 1997

Journal of Biological Chemistry

173

110

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Differential expression of VEGF isoforms and VEGF164-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF164 in vascular permeability and angiogenesis during implantation

Halder

Zhao

Söker

et al. 2000

genesis

135

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Summary: The mechanism(s) by which localized vascular permeability and angiogenesis occur at the sites of implantation is not clearly understood. Vascular endothelial growth factor (VEGF) is a key regulator of vasculogenesis during embryogenesis and angiogenesis in adult tissues. VEGF is also a vascular permeability factor. VEGF acts via two tyrosine kinase family receptors: VEGFR1 (Flt‐1) and VEGFR2 (KDR/Flk‐1). Recent evidence suggests that neuropilin‐1 (NRP1), a receptor involved in neuronal cell guidance, is expressed in endothelial cells, binds to VEGF165 and enhances the binding of VEGF165 to VEGFR2. We examined the spatiotemporal expression of vegf isoforms, nrp1 and vegfr2 as well as their interactions in the periimplantation mouse uterus. We observed that vegf164 is the predominant isoform in the mouse uterus. vegf164 mRNA accumulation primarily occurred in epithelial cells on days 1 and 2 of pregnancy. On days 3 and 4, the subepithelial stroma in addition to epithelial cells exhibited accumulation of this mRNA. After the initial attachment reaction on day 5, luminal epithelial and stromal cells immediately surrounding the blastocyst exhibited distinct accumulation of vegf164 mRNA. On days 6–8, the accumulation of this mRNA occurred in both mesometrial and antimesometrial decidual cells. These results suggest that VEGF164 is available in mediating vascular changes and angiogenesis in the uterus during implantation and decidualization. This is consistent with coordinate expression of vegfr2, and nrp1, a VEGF164‐specific receptor, in uterine endothelial cells. Their expression was low during the first 2 days of pregnancy followed by increases thereafter. With the initiation and progression of implantation (days 5–8), these genes were distinctly expressed in endothelial cells of the decidualizing stroma. Expression was more intense on days 6–8 at the mesometrial pole, the presumptive site of heightened angiogenesis and placentation. However, the expression was absent in the avascular primary decidual zone immediately surrounding the implanting embryo. Crosslinking experiments showed that 125I‐VEGF165 binds to both NRP1 and VEGFR2 present in decidual endothelial cells. These results suggest that VEGF164, NRP1 and VEGFR2 play a role in VEGF‐induced vascular permeability and angiogenesis in the uterus required for implantation. genesis 26:213–224, 2000. © 2000 Wiley‐Liss, Inc.

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VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung

et al. 2000

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We used whole lung cultures as a model to study blood vessel formation in vitro and to examine the role that epithelial‐mesenchymal interactions play during embryonic pulmonary vascular development. Mouse lungs were isolated at embryonic day 11.5 (E11.5) and cultured for up to 4 days prior to blood vessel analysis. Platelet endothelial cell adhesion molecule‐1 (PECAM/CD31) and thrombomodulin (TM/CD141) immunolocalization demonstrate that vascular development occurs in lung cultures. The vascular structures identified in lung cultures first appear as a loosely associated plexus of capillary‐like structures that with time surround the airways. To investigate the potential role of vascular endothelial cell growth factor (VEGF) during pulmonary neovascularization, we immunolocalized VEGF in embryonic lungs. Our data demonstrate that VEGF is uniformly present in the airway epithelium and the subepithelial matrix of E11.5 lungs. At later time points, E13.5 and E15.5, VEGF is no longer detected in the proximal airways, but is restricted to the branching tips of airways in the distal lung. RT‐PCR analysis reveals that VEGF164 is the predominant isoform expressed in lung cultures. Grafting heparin‐bound VEGF164 beads onto lung explants locally stimulates a marked neovascular response within 48 hr in culture. Semi‐quantitative RT‐PCR reveals an 18% increase in PECAM mRNA in VEGF164‐treated whole lung cultures as compared with untreated cultures. The restricted temporal and spatial expression of VEGF suggests that matrix‐associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways. © 2000 Wiley‐Liss, Inc.

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The Mouse Gene for Vascular Endothelial Growth Factor

Cited by 272 publications

References 42 publications

Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

Differential expression of VEGF isoforms and VEGF164-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF164 in vascular permeability and angiogenesis during implantation

VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung

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