Document Detail

FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription.
MedLine Citation:
PMID:  23319049     Owner:  NLM     Status:  MEDLINE    
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.
Sandrine Evellin; Federico Galvagni; Alessio Zippo; Francesco Neri; Maurizio Orlandini; Danny Incarnato; Daniela Dettori; Stefanie Neubauer; Horst Kessler; Erwin F Wagner; Salvatore Oliviero
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  Molecular and cellular biology     Volume:  33     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-07-05     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1198-209     Citation Subset:  IM    
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
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MeSH Terms
Capillaries / cytology,  metabolism*
Cell Adhesion / genetics
Cell Differentiation / genetics
Cell Line
Cell Movement / genetics
Down-Regulation / genetics
Embryonic Stem Cells / cytology,  metabolism
Endothelial Cells / cytology*,  metabolism*
Endothelium, Vascular / metabolism
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Integrin alphaVbeta3 / genetics,  metabolism,  physiology*
Neovascularization, Pathologic / metabolism
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins c-fos / genetics,  metabolism,  physiology*
Proto-Oncogene Proteins c-jun / genetics,  metabolism
Sp1 Transcription Factor / genetics,  metabolism
Transcription, Genetic
Vitronectin / genetics,  metabolism
Reg. No./Substance:
0/Integrin alphaVbeta3; 0/JunD protein, human; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Sp1 Transcription Factor; 0/Vitronectin; 0/fos-related antigen 1

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