title: FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription.
abstract: To form three-dimensional capillary tubes, endothelial cells must establish contacts with the extracellular matrix that provides signals for their proliferation, migration, and differentiation. The transcription factor Fosl1 plays a key role in the vasculogenic and angiogenic processes as Fosl1 knockout embryos die with vascular defects in extraembryonic tissues. Here, we show that Fosl1(-/-) embryonic stem cells differentiate into endothelial cells but fail to correctly assemble into primitive capillaries and to form tube-like structures. FOSL1 silencing affects in vitro angiogenesis, increases cell adhesion, and decreases cell mobility of primary human endothelial cells (HUVEC). We further show that FOSL1 is a repressor of αv and β3 integrin expression and that the down-modulation of αvβ3 rescues the angiogenic phenotype in FOSL1-silenced HUVEC, while the ectopic expression of αvβ3 alone reproduces the phenotypic alterations induced by FOSL1 knockdown. FOSL1 represses the transcription of both αv and β3 integrin genes by binding together with JunD to their proximal promoter via the transcription factor SP1. These data suggest that FOSL1-dependent negative regulation of αvβ3 expression on endothelial cells is required for endothelial assembly into vessel structures.
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors: Sandrine
authors: S
authors: Evellin
authors: Federico
authors: F
authors: Galvagni
authors: Alessio
authors: A
authors: Zippo
authors: Francesco
authors: F
authors: Neri
authors: Maurizio
authors: M
authors: Orlandini
authors: Danny
authors: D
authors: Incarnato
authors: Daniela
authors: D
authors: Dettori
authors: Stefanie
authors: S
authors: Neubauer
authors: Horst
authors: H
authors: Kessler
authors: Erwin F
authors: EF
authors: Wagner
authors: Salvatore
authors: S
authors: Oliviero
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D019096:Vitronectin / Q000235:genetics / Q000378:metabolism; D000099169:Fos-Related Antigen 1
chemical_list: D039302:Integrin alphaVbeta3; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; D019096:Vitronectin; D000099169:Fos-Related Antigen 1; C559371:JunD protein, human