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http://purl.uniprot.org/citations/18787186http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18787186http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Recently, we reported that the forkhead transcription factor, FKHR/FOXO1, is required for vascular endothelial growth factor (VEGF)-mediated upregulation of a number of genes in endothelial cells. Here, we tested the hypothesis that hepatocyte growth factor (HGF), a potent activator of PI3K-Akt in endothelial cells, is capable of depleting the nucleus of FKHR/FOXO1 and thus inhibiting VEGF induction of this class of genes.

Methods and results

Incubation of human coronary artery endothelial cells with HGF induced prolonged PI3K/Akt-dependent phosphorylation and nuclear exclusion of FKHR/FOXO1. HGF-mediated inhibition of FKHR/FOXO1 activity resulted in secondary attenuation of VEGF-induced expression of FKHR/FOXO1-dependent genes including vascular cell adhesion molecule-1, manganese superoxide dismutase, endothelial specific molecule-1, CBP/p300 interacting transactivator with ED-rich tail-2, bone morphogenetic protein-2, matrix metalloproteinase (MMP)-10, and MGC5618. At a functional level, preincubation of HGF resulted in inhibition of VEGF-induced vascular cell adhesion molecule (VCAM)-1-mediated monocyte adhesion to endothelial cells. HGF-mediated inhibition of VEGF-inducible VCAM-1 expression and monocyte adhesion was reversed by overexpression of constitutively active phosphorylation-resistant triple mutant (TM)-FKHR.

Conclusions

These findings suggest that physiological agonists of PI3K-Akt signaling pathway may modulate VEGF-FKHR/FOXO1-dependent gene expression in endothelial cells. The data underscore the importance of the "set point" of the endothelial cell when considering mechanisms of signal transduction."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.108.175109"xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Minami T."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Shih S.C."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Abid M.R."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Nadeau R.J."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Aird W.C."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/author"Spokes K.C."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/pages"2042-2048"xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/title"Hepatocyte growth factor inhibits VEGF-forkhead-dependent gene expression in endothelial cells."xsd:string
http://purl.uniprot.org/citations/18787186http://purl.uniprot.org/core/volume"28"xsd:string
http://purl.uniprot.org/citations/18787186http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18787186
http://purl.uniprot.org/citations/18787186http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18787186
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http://purl.uniprot.org/uniprot/#_A8K6K9-mappedCitation-18787186http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18787186
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