microscopic image of blood vessels

What is VEGF?

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 PDGF?

Platelet-derived growth factors (PDGFs) are disulfide-linked dimeric growth factors. PDGFs are potent mitogens for a variety of cell types, including smooth muscle cells, connective tissue cells, bone and cartilage cells, and some blood cells. PDGFs are stored in platelet α-granules and are released upon platelet activation. PDGFs are involved in many biological processes, including hyperplasia, chemotaxis, embryonic neuron development, and respiratory tubule epithelial cell development.

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 of VEGF family properties

Table 1. VEGF proteins, expression and functions in tissue, and receptors

 

VEGF name, synonymsExpression (partial list)FunctionReceptors (selected list)
VEGF-A121 Vascular Permeability Factor (VPF)all vascularized tissuesangiogenesis, induces endothelial cell proliferation, cell migration, osteoclastogenesisVEGFR-1, -2
VEGF-A145 Vascular Permeability Factor (VPF)all vascularized tissuesangiogenesis, induces endothelial cell proliferation, vasculogenesis, permeabilization of blood vessels, osteoclastogenesisVEGFR-1, -2, HSPG, Neuropilin-1
VEGF-A165 Vascular Permeability Factor (VPF)all vascularized tissuesangiogenesis, induces endothelial cell proliferation, vasculogenesis, permeabilization of blood vessels, osteoclastogenesisVEGFR-1, -2, HSPG, Neuropilin-1, -2
VEGF-A189 Vascular Permeability Factor (VPF)all vascularized tissuesangiogenesis, induces endothelial cell proliferation and migrationHSPG, Neuropilin-1, -2
VEGF-A206 Vascular Permeability Factor (VPF)all vascularized tissuesundeterminedHSPG, Neuropilin-1, -2
VEGF-B167 VEGF-Related Factor (VRF)heart, skeletal muscle, vascular smooth muscle cellsembryonic angiogenesisVEGFR-1, Neuropilin-1
VEGF-B186 VEGF-Related Factor (VRF)heart, skeletal muscle, vascular smooth muscle cellsembryonic angiogenesisVEGFR-1, Neuropilin-1
VEGF-C, VEGF-2, Vascular Endothelial Growth Factor Related protein (VRP), Flt4-Ligandneuroendocrine organs, lung, heart, kidney, vascular smooth muscle cellslymphangiogenesis and tumor angiogenesisVEGFR-2, -3, Neuropilin-2
VEGF-D, c-Fos Induced Growth Factor (FIGF)neuroendocrine organs, lung, lung, heart, kidney, vascular smooth muscle cellslymphangiogenesis and tumor angiogenesisVEGFR-2, -3
VEGF-E (Orf Virus)virus-derivedinduces endothelial proliferation, vascular permeability, angiogenesisVEGFR-2, Neuropilin-1 (binds NZ2-VEGF-E variant)
VEGF-F (Snake venom)snake venominduces endothelial proliferation, vascular permeability, angiogenesisVEGFR-2
PlGF-1 Placenta Growth Factor-1, PGFL, PGF, PIGFplacenta, thyroid, lung, goiterangiogenesis, chemotactic towards monocytes, wound healing and tumor formationVEGFR-1
PlGF-2 Placenta Growth Factor-2, PGFLplacenta, thyroid, lung, goiterangiogenesis, chemotactic towards monocytes, wound healing and tumor formationVEGFR-1, Neuropilin-1, Neuropilin-2
PlGF-3 Placenta Growth Factor-3, PGFLplacentaangiogenesis, chemotactic towards monocytes, wound healing and tumor formationVEGFR-1
PlGF-4 Placenta Growth Factor-4, PGFLplacenta, thyroid, lung, goiterangiogenesis, chemotactic towards monocytes, wound healing and tumor formationVEGFR-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 of PDGF family properties

Table 2. PDGF proteins, expression and functions in tissue, and receptors

PDGF name, synonymsExpression (partial list)FunctionReceptors (selected list)
PDGF-AA Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF)a-granules, released upon platelet activationmitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesisPDGFR-a
PDGF-BB Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF)heart, brain (substantia nigra), placenta, fetal kidneymitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesisPDGFR-a, PDGFR-b
PDGF-AB Glioma-Derived Growth Factor (GDGF), Osteosarcoma-Derived Growth Factor (ODGF)a-granules, released upon platelet activationmitogenic factor, hyperplasia, cell migration, embryonic neuron development, angiogenesisPDGFR-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, uterusmitogenic factor, hyperplasia, cell migration, embryonic development, angiogenesisPDGFR-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 intestinemitogenic factor, hyperplasia, cell migration, embryonic development, angiogenesisPDGFR-b
References
  1. 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. 
  2. 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. 
  3. Kazlauskas, A (2017) PDGFs and their receptors. Gene 614:1–7. 
Related products
Recombinant VEGF proteins VEGF antibodies 
PDGF proteinsPDGF antibodies
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