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The basic helix-loop-helix transcription factor HESR1 regulates endothelial cell tube formation.
A M Henderson1, S J Wang, A C Taylor
1Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California 92697, USA.
The Journal of Biological Chemistry
|November 9, 2000
Summary
HESR1 is crucial for new blood vessel formation. Its expression must decrease for initial growth and increase for network maturation, impacting vascular endothelial growth factor receptor-2 (VEGFR2) signaling.
Area of Science:
- Molecular Biology
- Cell Biology
- Vascular Biology
Background:
- Human endothelial cells form capillary-like networks in vitro.
- Representational difference analysis identifies genes in new blood vessel formation.
Purpose of the Study:
- Identify genes involved in new blood vessel formation.
- Investigate the role of HESR1 in endothelial cell network formation.
Main Methods:
- In vitro endothelial cell culture in collagen gels.
- Representational difference analysis.
- Overexpression and antisense oligonucleotide studies of HESR1.
- Quantitative analysis of gene expression (VEGFR2 mRNA).
Main Results:
- HESR1 (a basic helix-loop-helix protein) is induced during capillary-like network formation.
- HESR1 overexpression down-regulates VEGFR2, blocking proliferation, migration, and network formation.
- HESR1 knockdown via antisense oligonucleotides also inhibits network formation.
- HESR1 expression is altered in various tumors.
Conclusions:
- HESR1 plays a dual role in angiogenesis: down-regulation is needed for initial vessel budding and growth, while re-expression is essential for network formation and maintenance.
- HESR1 acts as a temporal regulator of vascular endothelial cell growth factor receptor-2 (VEGFR2)-mediated processes.
- Altered HESR1 expression suggests its involvement in tumor angiogenesis.