Forkhead transcription factors regulate expression of the chemokine receptor CXCR4 in endothelial cells and CXCL12-induced cell migration.
Foxc1 and Foxc2 transcription factors are required for vascular development. However, the molecular mechanisms by which Foxc1 and Foxc2 control angiogenesis, the growth of new blood vessels from pre-existing vessels and capillaries, remain unknown. CXC chemokine ligand 12 (CXCL12) and its receptor, CXCR4, are critical for the process of angiogenesis, including the migration and tube formation of endothelial cells. Here we show that Foxc1 and Foxc2 directly induce CXCR4 expression by activating its promoter in endothelial cells. Furthermore, Foxc1-deficient endothelial cells show a significant reduction in CXCR4 expression as well as CXCL12-stimulated migration. Taken together, these results provide novel evidence that Foxc transcription factors are important regulators of the chemotactic motility of endothelial cells through the induction of CXCR4 expression.
Hayashi
Hisaki
H
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA.
Kume
Tsutomu
T
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018014:Gene Transfer Techniques; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; D019718:Receptors, CXCR4; C082078:mesenchyme fork head 1 protein