Official websites use. Share sensitive information only on official, secure websites. Vascular endothelial growth factor A VEGF-A is a potent secreted mitogen critical for physiological and pathological angiogenesis. Regulation of VEGF-A occurs at multiple levels, including transcription, mRNA stabilization, splicing, translation and differential cellular localization of various isoforms. In this report, we show that the expression of different VEGF-A isoforms is regulated by a small upstream open reading frame uORF located within an internal ribosome entry site, which is translated through a cap-independent mechanism.
The growth of blood vessels, a process known as angiogenesis, is essential for organ growth and repair. An imbalance in this process contributes to numerous inflammatory, ischemic, immune and malignant disorders. The vascular endothelial growth factor A VEGF-A is a growth and survival factor for endothelial cells, playing an essential role in numerous physiological and pathological angiogenic processes throughout embryonic development and during adulthood 1 , 2.
In the quiescent vasculature of adult organs, VEGF is produced at basal level and protects endothelial cells from apoptosis. However, in a number of physiological situations, such as oestrus in the female reproductive organs, wound repair, adaptation to hypoxia as well as in many pathological situations like proliferative retinopathies, arthritis, psoriasis and of course cancer, VEGF level increases 3—5.
VEGF acts as the key mediator of tumor angiogenesis by stimulating the growth of new blood vessels from nearby capillaries and providing tumors with access to oxygen and nutrients they need to grow and metastasis.
These experiments on transgenic mice have clearly demonstrated that the expression level of VEGF is under very tight regulatory control, at least during development. Numerous studies have been devoted to understand the regulation of expression of this factor. The importance of regulating VEGF expression is further demonstrated by comparative genomic sequence analyses, which reveal the conservation of regulatory elements throughout numerous species. These elements are summarized in Figure 1.
