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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Fosl1 controls the assembly of endothelial cells into capillary tubes by direct repression of αv and β3 integrin transcription
Molecular and Cellular Biology, Volume 33, No. 6, Year 2013
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Description
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. © 2013, American Society for Microbiology.
Authors & Co-Authors
Evellin, Sandrine
Italy, Siena
Università Degli Studi Di Siena
Galvagni, Federico
Italy, Siena
Università Degli Studi Di Siena
Zippo, Alessio
Italy, Siena
Università Degli Studi Di Siena
Neri, Francesco
Italy, Siena
Università Degli Studi Di Siena
Italy, Torino
Human Genetics Foundation
Orlandini, Maurizio O.
Italy, Siena
Università Degli Studi Di Siena
Incarnato, Danny
Italy, Siena
Università Degli Studi Di Siena
Italy, Torino
Human Genetics Foundation
Dettori, Daniela
Italy, Torino
Human Genetics Foundation
Neubauer, Stefanie
Germany, Munich
Technische Universität München
Kessler, Horst
Germany, Munich
Technische Universität München
Saudi Arabia, Jeddah
King Abdulaziz University
Wagne, Erwin F.
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Oliviero, Salvatore
Italy, Siena
Università Degli Studi Di Siena
Italy, Torino
Human Genetics Foundation
Statistics
Citations: 44
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1128/MCB.01054-12
ISSN:
02707306
e-ISSN:
10985549
Research Areas
Cancer