Post-transcriptional Regulation of VEGF-A
Vascular Endothelial Growth Factor A (VEGF-A) is a secreted growth and survival factor that binds to endothelial cells and plays a critical role in the induction of angiogenic processes. It is essential for embryonic development and during adulthood plays
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Post-transcriptional Regulation of VEGF-A Hervé Prats and Christian Touriol
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Introduction
Vascular Endothelial Growth Factor A (VEGF-A) is a protein of critical importance in embryonic development and during adulthood. Even a slight variation in its normal level can have serious physiological consequences and as a result its expression is stringently regulated at every conceivable stage. Thus, the expression of VEGF-A represents a useful model that demonstrates gene regulation at its most sophisticated. VEGF-A acts on endothelial cells where it is required for cell survival, growth and migration. It is the main protein involved in the induction of angiogenesis, the formation of new blood vessels, and is therefore essential for adult organ growth and repair. VEGF-A plays an important role in physiological situations that affect blood vessels, such as the menstrual cycle, wound repair, adaptation to hypoxia and, importantly, embryonic development (Carmeliet 2005a; Ferrara 2005). Various pathological conditions also show elevated VEGF-A levels, such as proliferative retinopathies, arthritis, psoriasis and cancer (Ferrara 1999, 2002; Folkman 1995). In cancer, VEGF-A is crucial for tumor development since it stimulates the growth of new blood vessels from nearby capillaries (tumor angiogenesis), which allows tumor cells to acquire oxygen and nutrients and ultimately leads to metastasis. The importance of keeping tight control of VEGF-A expression has been clearly demonstrated in transgenic mice. Both the deletion of a single VEGF-A allele or the modest overexpression of VEGF-A result in defective vascularization and subsequent embryonic lethality (Carmeliet et al. 1996; Ferrara et al. 1996;
H. Prats • C. Touriol (*) Inserm UMR1037, Centre de Recherches en Cancérologie de Toulouse, ERL5294 CNRS, 2 avenue Hubert Curien, Oncopole entrée C, CS 53717, 31037 Toulouse Cedex 1, France Université Toulouse III Paul-Sabatier, Toulouse, France e-mail: [email protected] © Springer International Publishing Switzerland 2016 K.M.J. Menon, A.C. Goldstrohm (eds.), Post-transcriptional Mechanisms in Endocrine Regulation, DOI 10.1007/978-3-319-25124-0_8
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Miquerol et al. 2000). In addition, conditional gain and loss of function experiments in the erythroid lineage have demonstrated that alteration of VEGF-A levels during development significantly affects erythropoiesis in mouse embryos (Drogat et al. 2010). These studies emphasize the critical role of VEGF-A in developmental angiogenesis. In adult mice, tissue-specific overexpression of VEGF-A causes serious problems in processes such as angiogenesis and vascular hyperpermeability (Larcher et al. 1998), angioma formation and organ development (Dor et al. 2002), and can lead to severe proliferative retinopathy and retinal detachment (Ohno-Matsui et al. 2002). These results have been corroborated by conditional transgenic knock-out models of VEGF-A which also show impaired vascular functions (Eremina et al. 2008; Sivaskandarajah et al. 2011).
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