期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 33, 期 6, 页码 1198-1209出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01054-12
关键词
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资金
- Associazione Italiana Ricerca sul Cancro
- Regione Toscana Programma Salute
- Istituto Toscano Tumori
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 alpha v and beta 3 integrin expression and that the down-modulation of alpha v beta 3 rescues the angiogenic phenotype in FOSL1-silenced HUVEC, while the ectopic expression of alpha v beta 3 alone reproduces the phenotypic alterations induced by FOSL1 knockdown. FOSL1 represses the transcription of both alpha v and beta 3 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 alpha v beta 3 expression on endothelial cells is required for endothelial assembly into vessel structures.
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