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Details for messenger / hormone: VEGF-165

EndoNet ID: ENH00231

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Synonyms

  • VEGF
  • VEGF-165
  • VEGF(165)
  • vascular permeability factor
  • VPF
  • VEGFA
  • vascular endothelial growth factor A
  • vascular endothelial growth factor
  • VEGF165
  • 165 AA isoform of VEGF-A
  • vasculotropin

General information

  • Leptin significantly induced expression of vascular endothelial growth factor (VEGF). [1]
  • Vascular endothelial growth factor accounts for most of the angiogenic activity of adipose tissue. [2]
  • VEGF mRNA in adipocytes increase with rebound weight-gain after diet-restriction. [3]
  • Key regulator of blood vessel growth. [4]
  • Inflammatory cytokines such as IL1alpha and IL6 induce expression of VEGF in several cell types, including synovial fibroblast. VEGF may be a mediator of angiogenesis and permeability in inflammatory disorders. [4]
  • Cold-induced expression of the VEGF gene in brown adipose tissue is independent of thermogenic oxygen consumption. [5]
  • VEGF selectively up-regulates NRP1 but not NRP2 via the VEGF receptor 2-dependent pathway. [6]
  • Like PAF, VEGF-A(165) promotes translocation of P-selectin to the endothelial cell (EC) surface. [7]
  • VEGF(121) and VEGF(165) induced by hypoxia have different functions on coronary vascular growth. [8]
  • Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome. [9]
  • VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. [10]
  • Oncogenic mutations or amplification of Ras lead to VEGF upregulation. [4]
  • Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta. [11]
  • VEGF produced by tumor cells potently stimulates endothelial cell proliferation and angiogenesis and plays a key role in the pathophysiology of several neoplasias. [12]
  • VEGF is implicated in the pathogenesis of inflammatory joint diseases, including rheumatoid arthritis. [13]
  • Blockade of VEGF signaling can inhibit in vivo adipose tissue formation. [14]
  • White adipocytes are capable of producing VEGF in response to insulin and catecholamines. [15]
  • VEGF induces expression of the anti-apoptotic proteins Bcl-2 and A1 in endothelial cells. [4]

Classification

Hormone function

  • development and growth
    • growth stimulation

    Chemical classification

    • hormone
      • genome-encoded
        • cytokines
          • PDGF/VEGF growth factor family

      Composition

      VEGF165

      • Homodimer, disulfide-linked. Also found as heterodimer with PlGF. [16]
      Sequence 
      APMAEGGGQ NHHEVVKFM DVYQRSYCH 
PIETLVDIF QEYPDEIEY IFKPSCVPL 
MRCGGCCND EGLECVPTE ESNITMQIM 
RIKPHQGQH IGEMSFLQH NKCECRPKK 
DRARQENPC GPCSERRKH LFVQDPQTC 
KCSCKNTDS RCKARQLEL NERTCRCDK 
PRR
      UniProt P15692-4

      Links to other resources

      UniProt P15692-4
      Ensembl ENST00000372055
      KEGG hsa:7422

      • Anatomical structure: fat_cell

        • Several angiogenic factors are secreted by adipocytes, including recognised angiogenic signals like VEGF, PAI-1 and leptin, as well as putative signals such as metallothionein and haptoglobin. [17]
        • Hypoxia leads to an induction of leptin and VEGF expression in adipocytes, raising the likelihood that a low oxygen tension leads to the stimulation of angiogenesis in adipose tissue through the HIF-1 pathway. [17]

        Influenced by:

        • insulin receptor
          in fat_cell
          • The ability of insulin to stimulate VEGF formation by adipocytes suggests that the elevated circulating levels of insulin in obesity promote angiogenesis in adipose tissue as well as the enhanced accumulation of fat in human adipocytes. [18]

      • Anatomical structure: adipose_tissue

        • Several angiogenic factors are secreted by adipocytes, including recognised angiogenic signals like VEGF, PAI-1 and leptin, as well as putative signals such as metallothionein and haptoglobin. [17]

      • Anatomical structure: smooth_muscle_cell

        • VEGF is produced by cultured vascular smooth muscle cells. [19]

      • Anatomical structure: bone_marrow

        • VEGF, its receptors (VEGFR-1, VEGFR-2) and neuropillin-1 (NRP-1) are expressed at variable levels in bone marrow. [20]

      • Anatomical structure: osteoblast

      • Anatomical structure: cell_of_endometrium_of_uterus

        • VEGF stimulates capillary endothelial mitogenesis and morphogenesis in endometrium. [11]

        Influenced by:

        • ER-alpha
          in cell_of_endometrium_of_uterus
          • 17beta-estradiol (E2) directly regulates VEGF gene transcription in endometrial cells. [11]
          • A 2-fold increase in steady-state VEGF mRNA was evident after 15 h of E2. [11]
        • ER-beta
          in cell_of_endometrium_of_uterus
          • A 2-fold increase in steady-state VEGF mRNA was evident after 15 h of E2. [11]
          • 17beta-estradiol (E2) directly regulates VEGF gene transcription in endometrial cells. [11]

      • Anatomical structure: ovary

      • Anatomical structure: corpus_luteum

        • The luteal tissue is the major site of Ang II, ACE, AT1R, and VEGF. [21]

      • Anatomical structure: granulosa_cell

      • Anatomical structure: theca_cell

      • Anatomical structure: tertiary_follicle

      • Anatomical structure: lung

      • Anatomical structure: bronchial_epithelial_cell

      • Anatomical structure: epithelial_cell_with_microvilli

      • Anatomical structure: hepatocyte

        • VEGF protein was strongly expressed in both well-differentiated HCC cells and non-cancerous hepatocytes. [22]

      • Anatomical structure: preadipocyte

        Influenced by:

        • leptin receptor
          in preadipocyte
          • Leptin induced VEGF mRNA expression in cultured pre-adipocytes but not in adipocytes. [23]

      • Anatomical structure: mast_cell

        Influenced by:

        • CRF-R1
          in mast_cell
          • Activation of corticotropin-releasing hormone receptor 1 leeds to selective release of VEGF without granulation.

      • Anatomical structure: Müllers_radial_cell_of_retina

      • Anatomical structure: retina

        Influenced by:

        • Vascular endothelial growth factor receptor 2
          in continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics

      Targets

      Cellglypican 1neuropilin 1neuropilin-2sVEGF-R1Vascular endothelial growth factor receptor 1Vascular endothelial growth factor receptor 2
      blood vessel Present
      Phenotypes
      • excess of capillary formation
      • patterning of blood vessels
      bone marrow Present
      		Present
      		Present
      Phenotypes
      • hematopoiesis
      		Present
      Phenotypes
      • angiogenesis
      brain Present
      		Present
      Phenotypes
      • axon guidance
      		Present
      		Present
      breast Present
      continuous vascular endothelial cell of blood vessels and lymphatics Present
      Phenotypes
      • regulation of angiogenesis
      • positive regulation of endothelial cell proliferation
      • positive regulation of endothelial cell migration
      • inflammation
      Influences
      • ↑ interleukin 6
      		Present
      Influences
      • ↓ VEGF-165
      glomerulus Present
      Phenotypes
      • induction of podocyte apoptosis
      • formation of glomerular filter barrier
      • inhibition of glomerular capillary lumen development
      • patterning of blood vessels
      • positive regulation of apoptosis
      heart Present
      Phenotypes
      • patterning of blood vessels
      		Present
      		Present
      Phenotypes
      • heart development
      kidney Present
      Phenotypes
      • inhibition of ureteric bud branching
      • excess of endothelial cells
      • podocyte differentiation
      • cell differentiation
      • acute nephrotic range proteinuria
      		Present
      		Present
      lung Present
      		Present
      		Present
      mammary gland Present
      		Present
      microvascularendothelial cell Present
      Influences
      • ↑ von Willebrand factor
      Müllers radial cell of retina Present
      Phenotypes
      • regulation of neural retina development
      		Present
      Phenotypes
      • regulation of neural retina development
      neuron Present
      Phenotypes
      • axon guidance
      ovary Present
      pancreas Present
      placenta Present
      		Present
      		Present
      Phenotypes
      • preeclampsia
      podocyte Present
      		Present
      propria mucosa of bronchus Present
      sinusoidal endothelial cell Present
      Phenotypes
      • negative regulation of apoptosis
      		Present
      Phenotypes
      • regulation of endothelial cell differentiation
      skeleton muscle Present
      		Present
      smooth muscle Present
      Phenotypes
      • vessel maturation
      vascularendothelial cell Present
      Phenotypes
      • regulation of angiogenesis
      		Present
      		Present
      Phenotypes
      • vasculogenesis
      • vascular permeability
      Reference