title: Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation.
abstract: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube length by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions.
authors.affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Sho
authors.initials: S
authors.lastname: Tokumaru
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hanakawa
authors.forename: Ken
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shirakata
authors.forename: Xiuju
authors.initials: X
authors.lastname: Dai
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tohyama
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Koji
authors.initials: K
authors.lastname: Sayama
mesh_terms: D021581:Active Transport, Cell Nucleus; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D042601:Lymphatic Vessels / Q000166:cytology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A