Vascular endothelial growth factor (VEGF) is a potent growth and angiogenic cytokine. It stimulates proliferation and survival of endothelial cells and promotes angiogenesis and vascular permeability. Expressed in vascularized tissues, VEGF plays a prominent role in normal and pathological angiogenesis. Substantial evidence implicates VEGF in the induction of tumor metastasis and intra-ocular neovascular syndromes.
What is VEGF?
VEGF is a signal protein that stimulates the formation of blood vessels, playing a critical role in both normal and pathological angiogenesis. VEGF release can be triggered by various factors, including hypoxia (low oxygen levels), inflammation, and the presence of certain growth factors and cytokines. While VEGF is essential for normal physiological processes like wound healing and the formation of the circulatory system during embryonic development, it can also contribute to pathological conditions such as cancer, where it promotes tumor growth and metastasis by enhancing blood supply. Thus, VEGF can be both beneficial and detrimental, depending on the context and balance within the biological system.
What is platelet-derived growth factor (PDGF)?
Platelet-Derived Growth Factor (PDGF) is a protein that plays a significant role in regulating cell growth and division, and it is characterized as a disulfide-linked dimeric growth factor. PDGF functions by stimulating the proliferation and differentiation of various cell types, including smooth muscle cells, connective tissue cells, bone and cartilage cells, and some blood cells, which are essential for wound healing and tissue repair. PDGFs are potent mitogens and are stored in platelet α-granules, being released upon platelet activation. In cell culture, PDGF is used to enhance the growth and survival of cells, particularly those involved in connective tissue formation and maintenance. PDGFs are involved in numerous biological processes such as hyperplasia, chemotaxis, embryonic neuron development, and respiratory tubule epithelial cell development, making them valuable tools for studying cellular processes and developing therapeutic applications in regenerative medicine and tissue engineering.
Biochemical properties of VEGF and PDGF
The VEGF/PDGF super gene family of growth factors is characterized by the presence of eight conserved cysteine residues forming disulfide linked dimers. Two representatives examples are below:
Human VEGF165 is a 38.2 kDa, disulfide-linked homodimeric protein comprising two 165 amino acid polypeptide chains.
Human PDGF-AB is a 26.4 kDa disulfide-linked heterodimer, comprising one α chain and one β chain (234 total amino acids).
Applications of VEGFs in biomedical research
VEGF recombinant proteins are used in multiple research capacities. For instance, recombinant VEGF-165 has been used in:
- Examining signaling pathways contributing to upregulation of macrophage inhibitory factor (MIF) in U-87 MG cells
- In vivo subcutaneous angiogenesis assays to study blood vessel development for tumor cell growth [1]
- hPSC derived mesoderm cell culture for mesoderm induction and downstream cellular differentiation [2]
Properties of VEGF
VEGF signals through three receptors; fms-like tyrosine kinase (flt-1), KDR gene product (the murine homolog of KDR is the flk-1 gene product) and the flt4 gene product.
Table 1. VEGF proteins, expression and functions in tissue, and receptors
| VEGF name, synonyms | Expression (partial list) | Function | Receptors (selected list) |
|---|---|---|---|
| VEGF-A121 Vascular Permeability Factor (VPF) | all vascularized tissues | angiogenesis, induces endothelial cell proliferation, cell migration, osteoclastogenesis | VEGFR-1, -2 |
| VEGF-A145 Vascular Permeability Factor (VPF) | all vascularized tissues | angiogenesis, induces endothelial cell proliferation, vasculogenesis, permeabilization of blood vessels, osteoclastogenesis | VEGFR-1, -2, HSPG, Neuropilin-1 |
| VEGF-A165 Vascular Permeability Factor (VPF) | all vascularized tissues | angiogenesis, induces endothelial cell proliferation, vasculogenesis, permeabilization of blood vessels, osteoclastogenesis | VEGFR-1, -2, HSPG, Neuropilin-1, -2 |
| VEGF-A189 Vascular Permeability Factor (VPF) | all vascularized tissues | angiogenesis, induces endothelial cell proliferation and migration | HSPG, Neuropilin-1, -2 |
| VEGF-A206 Vascular Permeability Factor (VPF) | all vascularized tissues | undetermined | HSPG, Neuropilin-1, -2 |
| VEGF-B167 VEGF-Related Factor (VRF) | heart, skeletal muscle, vascular smooth muscle cells | embryonic angiogenesis | VEGFR-1, Neuropilin-1 |
| VEGF-B186 VEGF-Related Factor (VRF) | heart, skeletal muscle, vascular smooth muscle cells | embryonic angiogenesis | VEGFR-1, Neuropilin-1 |
| VEGF-C, VEGF-2, Vascular Endothelial Growth Factor Related protein (VRP), Flt4-Ligand | neuroendocrine organs, lung, heart, kidney, vascular smooth muscle cells | lymphangiogenesis and tumor angiogenesis | VEGFR-2, -3, Neuropilin-2 |
| VEGF-D, c-Fos Induced Growth Factor (FIGF) | neuroendocrine organs, lung, lung, heart, kidney, vascular smooth muscle cells | lymphangiogenesis and tumor angiogenesis | VEGFR-2, -3 |
| VEGF-E (Orf Virus) | virus-derived | induces endothelial proliferation, vascular permeability, angiogenesis | VEGFR-2, Neuropilin-1 (binds NZ2-VEGF-E variant) |
| VEGF-F (Snake venom) | snake venom | induces endothelial proliferation, vascular permeability, angiogenesis | VEGFR-2 |
| PlGF-1 Placenta Growth Factor-1, PGFL, PGF, PIGF | placenta, thyroid, lung, goiter | angiogenesis, chemotactic towards monocytes, wound healing and tumor formation | VEGFR-1 |
| PlGF-2 Placenta Growth Factor-2, PGFL | placenta, thyroid, lung, goiter | angiogenesis, chemotactic towards monocytes, wound healing and tumor formation | VEGFR-1, Neuropilin-1, Neuropilin-2 |
| PlGF-3 Placenta Growth Factor-3, PGFL | placenta | angiogenesis, chemotactic towards monocytes, wound healing and tumor formation | VEGFR-1 |
| PlGF-4 Placenta Growth Factor-4, PGFL | placenta, thyroid, lung, goiter | angiogenesis, chemotactic towards monocytes, wound healing and tumor formation | VEGFR-1 |
Applications of PDGFs in biomedical research
- PDGF-BB stimulates cell proliferation and osteogenic differentiation of stem cells through the ERK pathway
- PDGF-BB stimulates cell proliferation and osteogenic differentiation of stem cells through the ERK pathway
- PDGF-AA supplementation supports in vitro functionality of dermal papilla cells.
Properties of PDGF
Two distinct signaling receptors used by PDGFs have been identified and named PDGFR-α and PDGFR-β. PDGFR-α is a high-affinity receptor for each of the three PDGF forms. On the other hand, PDGFR-β interacts with only PDGF-BB and PDGF-AB.
Table 2. PDGF proteins, expression and functions in tissue, and receptors
| PDGF name, synonyms | Expression (partial list) | Function | Receptors (selected list) |
|---|---|---|---|
| PDGF-AA Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF) | a-granules, released upon platelet activation | mitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesis | PDGFR-a |
| PDGF-BB Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF) | heart, brain (substantia nigra), placenta, fetal kidney | mitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesis | PDGFR-a, PDGFR-b |
| PDGF-AB Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF) | a-granules, released upon platelet activation | mitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesis | PDGFR-a, PDGFR-b |
| PDGF-CC Fallotein, Spinal Cord-Derived Growth Factor (SCDGF) | retinal pigment epithelia, fallopian tube, vascular smooth muscle cells in kidney, platelets, prostate, testis, uterus | mitogenic factor, hyperplasia, cell migration, embryonic development, angiogenesis | PDGFR-a |
| PDGF-DD Iris-Expressed Growth Factor (IEGF), Spinal Cord-Derived Growth Factor-B (SCDGF-B) | heart, pancreas, adrenal gland, ovary, placenta, liver, kidney, prostate, testis, small intestine | mitogenic factor, hyperplasia, cell migration, embryonic development, angiogenesis | PDGFR-b |
Vascular endothelial growth factor and platelet-derived growth factor
VEGF and PDGF are essential in research and therapeutic applications for their ability to enhance and maintain cell growth and improve culture conditions.
Learn more about:
Recombinant VEGF proteins
VEGF antibodies
PDGF proteins
PDGF antibodies
References
- Lechertier T, Reynolds LE, Kim H, et al. (2020) Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth. Nat Commun 11: 2810.
- Bruveris FF, Ng ES, Stanley EG, et al. (2021) VEGF, FGF2, and BMP4 regulate transitions of mesoderm to endothelium and blood cells in a human model of yolk sac hematopoiesis. Exp Hematol 103:30-39.e2.
- Kazlauskas, A (2017) PDGFs and their receptors. Gene 614:1–7.