title: The transcription factor Grainyhead like 3 (GRHL3) affects endothelial cell apoptosis and migration in a NO-dependent manner.
abstract: Migratory capacity and resistance to apoptosis are crucial for proper endothelial function. In a screen for anti-apoptotic genes in a breast cancer cell line, we identified Grainyhead like 3 (GRHL3). Therefore, the aim of our study was to investigate whether GRHL3 is expressed in endothelial cells and moreover, to determine its role in migration, apoptosis and senescence. GRHL3 is expressed in human endothelial cells. GRHL3 is required for endothelial cell migration. The underlying mechanism is independent of vascular endothelial growth factor. GRHL3 induces Akt and endothelial nitric oxide synthase phosphorylation and its expression is increased by physiological concentrations of nitric oxide. Nitric oxide dependent migration is completely dependent on GRHL3 expression. Moreover, GRHL3 inhibits apoptosis of endothelial cells in an eNOS-dependent manner. Thus, loss of GRHL3 may result in endothelial dysfunction in vivo. One may consider new therapeutic strategies with the aim to conserve GRHL3 expression in the vasculature.
authors.affiliation: Department of Aging Research, IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany. Margarete.Lukosz@gmx.de
authors.forename: Margarete
authors.initials: M
authors.lastname: Lukosz
authors.forename: Arne
authors.initials: A
authors.lastname: Mlynek
authors.forename: Philip
authors.initials: P
authors.lastname: Czypiorski
authors.forename: Joachim
authors.initials: J
authors.lastname: Altschmied
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III