Identification of vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) promoter/enhancer sequences sufficient for angioblast and endothelial cell-specific transcription in transgenic mice
Abstract
The vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) is the first endothelial receptor tyrosine kinase to be expressed in angioblast precursors, and its function is essential for the differentiation of endothelial cells and hematopoietic precursors. We have identified cis-acting regulatory elements of the murine Flk-1 gene that mediate endothelium-specific expression of a LacZ reporter gene in transgenic mice. Sequences within the 5'-flanking region of the Flk-1 gene, in combination with sequences located in the first intron, specifically targeted transgene expression to angioblasts and endothelial cells of transgenic mice. The intronic regulatory sequences functioned as an autonomous endothelium-specific enhancer. Sequences of the 5'-flanking region contributed to a strong, uniform, and reproducible transgene expression and were stimulated by the transcription factor HIF-2alpha. The Flk-1 gene regulatory elements described in this study should allow the elucidation of the molecular mechanisms involved in endothelial cell differentiation and angiogenesis.
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Macrophage-secreted growth factors such as VEGF, VEGFR1, VEGFR2, PDGF, FGF, and TGF-β are induced by hypoxia.
“Macrophage-secreted growth factors such as vascular endothelial growth factor (VEGF) and its receptor VEGFR1 and VEGFR2, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor-β (TGF-β) have been reported to be induced by hypoxia [76,77,78].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [78]
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References 40 · Cited by 223
- Authors
- Kappel, A., Rönicke, V., Damert, A., Flamme, I., Risau, W., & Breier, G.
- Affiliations
- Max Planck Society (DE)
- From the Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany; the Zentrum für molekulare Medizin, Köln, Germany.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1999-06-15
- Volume
- 93
- Issue
- 12
- Pages
- 4284-4292
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1855965672
- Cited by
- 223
- References
- 40
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 5
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- VEGF receptor 2, Flk-1, angioblasts, endothelial cells, cis-regulatory elements, enhancers, 5'-flanking region, intronic enhancer, HIF-2α, transcriptional regulation, endothelial differentiation, angiogenesis, transgenic mice, lacZ reporter
- MeSH terms
- Animals, Aorta, Base Sequence, beta-Galactosidase, Cattle, Endothelium, Vascular, Enhancer Elements, Genetic, Introns, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Stem Cells, Transcription, Genetic, Yolk Sac, 3T3 Cells, Receptors, Growth Factor, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Mice
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