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FLASH GENE
Symbol PGF contributors: sge/npt/pgu - updated : 19-09-2016
HGNC name placental growth factor
HGNC id 8893
Location 14q24.3      Physical location : 75.408.539 - 75.422.291
Synonym name
  • placental growth factor-like
  • placental growth factor, vascular endothelial growth factor-related protein
  • Synonym symbol(s) PLGF, PIGF, PIGF-2, PIGF-3, PIGF-1, PGFL, SHGC-10760, D12S1900
    DNA
    TYPE functioning gene
    STRUCTURE 13.93 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   metal/iron
    text structure metal responsive elements located between -511 and -468bp in the promoter region are important for hypoxic regulation in trohpoblast-derived cells
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1848 - 149 placenta, colon, mammary carcinomas 1994 7929268
  • a 131 amino acids mature peptide
  • also called PIGF-1 or PIGF-131
  • 7 splicing 1758 19.3 170 . specific to early placenta (8 week) . remaining cell attached unless released by heparin 1994 7929268
  • a 152 amino acids mature peptide
  • binding to NRP1 and NRP2 in a heparin-dependent manner
  • containing a basic insert acting as a cell retention signal
  • insertion of C terminal stretch of 21 AA
  • also called PIGF-2 or PIGF-152
  • 7 splicing 1908 - 169 placenta 1994 7929268
  • a 203 amino acids mature peptide
  • homodimer and monomer
  • also called PIGF-3 or PIGF-203
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveliver   lowly
    Reproductivefemale systemplacenta  predominantly Homo sapiens
    Respiratorylung   moderately
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 18 amino acids signal peptide
  • two probable N-glycosylation sites
  • conjugated GlycoP
    mono polymer homomer , heteromer , monomer , dimer
    isoforms Precursor a 203 amino acids mature peptide
    HOMOLOGY
    interspecies homolog to C.elegans B0412.2
    homolog to rattus Pgf (63.58 pc)
    homolog to murine Pgf (66.89 pc)
    intraspecies homolog to vascular endothelial growth factor
    Homologene
    FAMILY
  • PDGF/VEGF family of growth factors
  • CATEGORY regulatory , secretory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    text secreted (the three forms)
    basic FUNCTION
  • ligand of FLT1 (receptor tyrosine kinase)
  • playing a role in angiogenesis
  • stimulating proliferation and migration of endothelial cells
  • inducing DNA synthesis
  • stimulating MAP kinase
  • having with VEGFA a functional role for recruitment of osteoprogenitor cells in the course of endochondral bone formation or remodeling
  • is required for mediating and coordinating numerous aspects of bone fracture repair
  • may protect erythroid progenitors from cytokine-induced inhibition of colony formation
  • inducing 5-lipoxygenase-activating protein to increase leukotriene formation in sickle cell disease, which in turn meidates both inflammation and airway hyperactivity
  • directly regulating the motility of lung cancer cells, regulation that is critically dependent on ROCK1
  • exogenous PGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following myocardial infarction
  • is a secreted factor that supports hypertrophy and cardiac function during pressure overload by affecting endothelial cells and fibroblasts that in turn stimulate and support the myocytes through additional paracrine factors
  • is a critical mediator of blood vessel formation
  • mediates angiogenesis in hypoxic pulmonary hypertension
  • plays a role in the promotion of hair growth and therefore may serve as an additional therapeutic target for the treatment of alopecia
  • associate with Epithelial-mesenchymal transition (EMT) in various cancers
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, replication
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text positif control of cell proliferation
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • heterodimer with VEGF/VEGF-A
  • antiparallel homodimer, disulfide-linked
  • INTERACTION
    DNA
    RNA
    small molecule other,
  • heparin binding (only PIGF-2 isoform)
  • protein
  • binding to the receptor tyrosine kinase FLT1
  • interacting with MMP9 (PGF–MMP9–expressing cells restore microcirculation and efficacy of cell therapy in aged dystrophic muscle)
  • HIF1A is an hypoxia-independent target of PGF
  • PGF-induced EGR1 regulates hypoxia-inducible factor-1alpha (HIF-1alpha) in endothelial cells
  • promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP13
  • in erythroid cells, expression of KLF1 precedes PGF, and its enforced expression in human erythroid progenitor cells induces PGF mRNA
  • could regulate the expression of EMT-related proteins and promote migration of siha cells through ERK/MAPK signaling pathway
  • may activate MMP9 via MAPK14 signaling pathway
  • cell & other
    REGULATION
    induced by hypoxia increases endothelial cells PLGF expression posttranscriptionally
    Other post-transcriptional regulation of placenta growth factor mRNA by hydrogen peroxide
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    acting as a survival factor for malignant mesothelioma cells
    tumoral     --over  
    increased expression in colorectal cancer
    constitutional     --low  
    lower in severe preeclampsia or eclampsia than in normal pregnancy
    constitutional     --other  
    significant correlation between expression of cell-free mRNA and PGF protein level in severe preeclampsia
    constitutional     --over  
    is associated with development of epilepsy
    constitutional     --low  
    concentration of PGF is lower in severe preeclampsia compared with normal pregnancy
    Susceptibility to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV)
    Variant & Polymorphism SNP
  • SNPs rs2268615 and rs2268614 were associated with nAMD
  • Candidate gene
  • enhanced expression of PGF and FLT1 may contribute to rheumatoid inflammation by triggering production of proinflammatory cytokines
  • PGF is linked to a poor prognosis in breast cancer
  • significant relationship between serum PGF level and maximum tumor size was detected in osteosarcoma
  • may participate in both tumor-associated angiogenesis and lymphangiogenesis of cervical carcinogenesis
  • Marker
  • with FLT1, is an effective biomarker in predicting PE (preeclampsia) during the second trimester, before the clinical onset of PE
  • Therapy target
    SystemTypeDisorderPubmed
    neuromuscular  
    PGF–MMP9–expressing cells restore microcirculation and efficacy of cell therapy in aged dystrophic muscle
    cancerangiogenesis 
    PGF neutralization with monoclonal antibodies does not decrease tumor angiogenesis
    cancer  
    PGF inhibition blocks vessel abnormalization rather than density in certain tumors and anti-PGF treatment lacks efficacy in some cancer models
    cancerlung 
    potential therapeutic target in lung cancer
    ANIMAL & CELL MODELS
  • Pgf knockout mice
  • Plgf-null mice showed altered bone repair leading to delayed unions
  • Pgf(-/-) mice rapidly died of heart failure within 1 week of pressure overload, they showed an inability to upregulate angiogenesis, and they showed significantly less fibroblast activity in the heart