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          Institute: MPI für Neurobiologie     Collection: Molecular Neurobiology     Display Documents



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ID: 126249.0, MPI für Neurobiologie / Molecular Neurobiology
Homeobox A9 transcriptionally regulates the EphB4 receptor to modulate endothelial cell migration and tube formation
Authors:Bruhl, T.; Urbich, C.; Aicher, D.; Acker-Palmer, Amparo; Zeiher, A.M.; Dimmeler, S.
Date of Publication (YYYY-MM-DD):2004-04-02
Title of Journal:Circulation Research
Journal Abbrev.:Circ. Res.
Volume:94
Issue / Number:6
Start Page:743
End Page:751
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Homeobox genes (Hox) encode for transcription factors, which regulate cell proliferation and migration and play an important role in the development of the cardiovascular system during embryogenesis. In this study, we investigated the role of HoxA9 for endothelial cell migration and angiogenesis in vitro and identified a novel target gene, the EphB4 receptor. Inhibition of HoxA9 expression decreased endothelial cell tube formation and inhibited endothelial cell migration, suggesting that HoxA9 regulates angiogenesis. Because Eph receptor tyrosine kinases importantly contribute to angiogenesis, we examined whether HoxA9 may transcriptionally regulate the expression of EphB4. Downregulation of HoxA9 reduced the expression of EphB4. Chromatin-immunoprecipitation revealed that HoxA9 interacted with the EphB4 promoter, whereas a deletion construct of HoxA9 without DNA-binding motif (Delta(aa) 206-272) did not bind. Consistently, HoxA9 wild-type overexpression activated the EphB4 promoter as determined by reporter gene expression. HoxA9 binds to the EphB4 promoter and stimulates its expression resulting in an increase of endothelial cell migration and tube forming activity. Thus, modulation of EphB4 expression may contribute to the proangiogenic effect of HoxA9 in endothelial cells.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Molecular Neurobiology (Klein)/Signal Transduction (Palmer)
External Affiliations:Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany
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