Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1).

ABSTRACT: Despite genetic evidence establishing angiopoietin-1 (Ang-1) as an essential regulator of vascular development, the molecular mechanisms underlying Ang-1 function are almost completely uncharacterized. In this report, we demonstrate that Ang-1, via Akt activation, is a potent inhibitor of the forkhead transcription factor FKHR (FOXO1), identifying for the first time a nuclear signaling pathway through which Ang-1 modulates gene expression. We use microarray analysis to show that FKHR, whose function in endothelial cells has not previously been elucidated, regulates many genes associated with vascular destabilization and remodeling (including angiopoietin-2, an Ang-1 antagonist) and endothelial cell apoptosis (e.g., survivin, TRAIL). Ang-1 inhibits FKHR-mediated changes in gene expression a

SUBMITTER: Daly C 

PROVIDER: S-EPMC406295 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature