Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis.
Angiogenesis, formation of new vessels from pre-existing ones, results from stimulation of endothelial cells, which line the vessel wall. These cells will leave their resting state and start to digest the basement membrane, proliferate, migrate and eventually differentiate to form a hollow tube. All these steps can be induced by growth factors and this review will focus on two important types of angiogenic growth factors, vascular endothelial growth factor (VEGF; also denoted vascular permeability factor, VPF) and fibroblast growth factor (FGF). Both types of factors bind to cell surface expressed receptors, which are ligand-stimulatable tyrosine kinases. Binding of the growth factors to their receptors leads to activation of the intrinsic tyrosine kinase and signal transduction to downstream signalling cascades. This results in transcriptional changes and biological responses. The molecular aspects of signalling cascades critical for endothelial cell proliferation and migration are beginning to be delineated. In contrast, signalling cascades leading to endothelial cell differentiation remain to be determined. Angiogenesis is essential for a number of physiological events such as embryonic development, ovulation, and wound healing. It has become increasingly clear that a number of diseases depend on angiogenesis. For future development of therapeutic tools, it is important to understand the molecular mechanisms that regulate angiogenesis.
Gerwins
P
P
Department of Genetics and Pathology, Rudbeck Laboratory, S-751 85, Uppsala, Sweden.
Sköldenberg
E
E
Claesson-Welsh
L
L
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy / Q000639:trends; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors