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Pbx1 is required for Hox D3-mediated angiogenesis
A Charboneau1, L East, N Mulholland
1Department of Surgery, University of California, San Francisco, 94143, USA.
Angiogenesis
|December 6, 2005
Summary
Pbx1 is essential for angiogenesis, promoting endothelial cell migration and blood vessel formation. This co-factor enhances the activity of Hox D3 transcription factors, crucial for blood vessel development.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Homeobox (Hox) D3 transcription factor promotes endothelial cell (EC) migration and angiogenesis by inducing alphavbeta3 integrin expression.
- Pbx co-factors enhance Hox factor binding to target DNA.
Purpose of the Study:
- To investigate the role of Pbx1, a co-factor for Hox factors, in angiogenesis.
- To determine if Pbx1 is required for the pro-angiogenic activity of Hox D3 in endothelial cells.
Main Methods:
- Analysis of Pbx1 isoform expression in endothelial cells (ECs).
- Electrophoretic mobility shift assays (EMSAs) to assess Pbx1/Hox DNA binding activity in nuclear extracts from angiogenic and quiescent ECs.
- In vivo angiogenesis assays using bFGF and anti-sense Pbx1 oligonucleotides.
- Quantitative analysis of beta3 integrin expression.
Main Results:
- Endothelial cells predominantly express the Pbx1b isoform.
- Active Pbx1 levels and Pbx1/Hox DNA complex formation were higher in angiogenic ECs compared to quiescent ECs.
- Anti-sense Pbx1 impaired Pbx1/Hox DNA binding, EC migration, and bFGF-induced angiogenesis in vivo.
- Beta3 integrin expression was reduced in the presence of anti-sense Pbx1, despite unchanged Hox D3 levels.
Conclusions:
- Pbx1 is a critical co-factor required for the pro-angiogenic DNA binding and transcriptional activity of Hox D3 in endothelial cells.
- Pbx1 plays a significant role in regulating endothelial cell migration and angiogenesis.