The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment. This homeostatic function of VEGFs has been less intensely studied than their involvement in disease processes, development, and reproduction, but they still play a substantial and significant role in healthy control of blood volume and pressure, interstitial volume and drainage, renal and lung function, immunity, and signal processing in the peripheral and central nervous system. The widespread expression of VEGFs in healthy adult tissues, and the disturbances seen when VEGF signaling is inhibited support this view of the proteins as endogenous regulators of normal physiological function. This review summarizes the evidence and recent breakthroughs in understanding of the physiology that is regulated by VEGF, with emphasis on the role they play in maintaining homeostasis. © 2017 American Physiological Society. Compr Physiol 8:955-979, 2018.
Comprehensive Physiology. 2018 Jun 18*** epublish ***
David O Bates, Nicholas Beazley-Long, Andrew V Benest, Xi Ye, Nikita Ved, Richard P Hulse, Shaney Barratt, Maria J Machado, Lucy F Donaldson, Steven J Harper, Maria Peiris-Pages, Domingo J Tortonese, Sebastian Oltean, Rebecca R Foster
Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom., School of Life Sciences, University of Nottingham, Nottingham, United Kingdom., Department of Pharmacology, University of Oxford, Oxford, United Kingdom., Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom., Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom., School of Physiology, Pharmacology & Neuroscience, Medical School, University of Bristol, Bristol, United Kingdom., Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., Centre for Comparative and Clinical Anatomy, University of Bristol, Bristol, United Kingdom., Institute of Biomedical & Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom., Bristol Renal, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.