Placental growth factor

Placental growth factor (PlGF) is a protein that in humans is encoded by the PGF gene.[5][6]

PGF
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPGF, D12S1900, PGFL, PLGF, PlGF-2, SHGC-10760, Placental growth factor, PIGF
External IDsOMIM: 601121 MGI: 105095 HomoloGene: 1978 GeneCards: PGF
Orthologs
SpeciesHumanMouse
Entrez

5228

18654

Ensembl

ENSG00000119630

ENSMUSG00000004791

UniProt

P49763

P49764

RefSeq (mRNA)

NM_002632
NM_001207012
NM_001293643

NM_001271705
NM_008827

RefSeq (protein)

NP_001193941
NP_001280572
NP_002623

NP_001258634
NP_032853

Location (UCSC)Chr 14: 74.94 – 74.96 MbChr 12: 85.21 – 85.22 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Placental growth factor (PGF) is a member of the VEGF (vascular endothelial growth factor) sub-family - a key molecule in angiogenesis and vasculogenesis, in particular during embryogenesis. The main source of PGF during pregnancy is the placental trophoblast. PGF is also expressed in many other tissues, including the villous trophoblast.[7]

The placental growth factor (PGF) gene is a protein-coding gene and a member of the vascular endothelial growth factor (VEGF) family. The PGF gene is expressed only in human umbilical vein endothelial cells (HUVE) and the placenta. PGF is ultimately associated with angiogenesis. Specifically, PGF plays a role in trophoblast growth and differentiation. Trophoblast cells, specifically extravillous trophoblast cells, are responsible for invading the uterine wall and the maternal spiral arteries. The extravillous trophoblast cells produce a blood vessel of larger diameter for the developing fetus that is independent of maternal vasoconstriction. This is essential for increased blood flow and reduced resistance.[8] Proper development of blood vessels in the placenta is crucial for the higher blood requirement of the fetus later in pregnancy. Under normal physiologic conditions, PGF is also expressed at a low level in other organs including the heart, lung, thyroid, and skeletal muscle.

Isoform tissue specificity

There are three isoforms of this protein: PGF-1, PGF-2, PGF-3. PGF-1 is specifically found in the colon as well as mammary carcinomas, while PGF-2 is only found in early placenta up until the 8th week of development. PGF-2 is the only isoform able to bind to heparin. PGF-3 is found mainly in placental tissues. [9] [10]

Clinical significance

Placental growth factor-expression within human atherosclerotic lesions is associated with plaque inflammation and neovascular growth.[11][12]

Serum levels of PGF and sFlt-1 (soluble fms-like tyrosine kinase-1, also known as soluble VEGF receptor-1) are altered in women with preeclampsia. Studies show that in both early and late onset preeclampsia, maternal serum levels of sFlt-1 are higher and PGF lower in women presenting with preeclampsia. In addition, placental sFlt-1 levels were significantly increased and PGF decreased in women with preeclampsia as compared to those with uncomplicated pregnancies. This suggests that placental concentrations of sFlt-1 and PGF mirror the maternal serum changes. This is consistent with the view that the placenta is the main source of sFlt-1 and PGF during pregnancy.1

PGF is a potential biomarker for preeclampsia, a condition in which blood vessels in the placenta are too narrow, resulting in high blood pressure. As mentioned before, extravillous trophoblast cells invade maternal arteries. Improper differentiation may result in hypo-invasion of these arteries and thus failure to widen enough. Studies have found low levels of PGF in women who were diagnosed with preeclampsia later in their pregnancy.

Associated diseases

Placental insufficiency, otherwise known as uteroplacental vascular insufficiency, results from insufficient blood supply to the placenta. This disease is characterized by an alteration in the PGF gene and its GPCR and ERK signaling pathways.[13] Alterations in the PGF and the PGF receptor mRNA expression prevent the normal development of placental vasculature.[14]

Twin-to-twin transfusion syndrome is another disease associated with the PGF gene. This is a rare disease occurring primarily in identical twins where blood from one twin is transferred to the other. Typically, the twin whose blood is being transferred is born smaller and with anemia while the other twin is born larger with too much blood and at increased risk for heart failure. The PGF gene pathways primarily affected are the TGF-Beta pathway and AKT signaling pathway.[15]

References
  1. GRCh38: Ensembl release 89: ENSG00000119630 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000004791 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PGF placental growth factor, vascular endothelial growth factor-related protein".
  6. Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG (April 1993). "Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14". Oncogene. 8 (4): 925–31. PMID 7681160.
  7. Khalil A, Muttukrishna S, Harrington K, Jauniaux E (July 2008). Lumbiganon P (ed.). "Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders". PLOS ONE. 3 (7): e2766. Bibcode:2008PLoSO...3.2766K. doi:10.1371/journal.pone.0002766. PMC 2447877. PMID 18648513.
  8. Carlson, Bruce (2009). Human Embryology and Developmental Biology. Elsevier. ISBN 978-0-323-05385-3.
  9. "UniProtKB - P49763 (PLGF_HUMAN)". UniProt.
  10. "Placental Growth Factor". Online Mendelian Inheritance in Man.
  11. Khurana R, Moons L, Shafi S, Luttun A, Collen D, Martin JF, Carmeliet P, Zachary IC (May 2005). "Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation" (PDF). Circulation. 111 (21): 2828–36. doi:10.1161/CIRCULATIONAHA.104.495887. PMID 15911697.
  12. Shibuya M (April 2008). "Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis". BMB Reports. 41 (4): 278–86. doi:10.5483/BMBRep.2008.41.4.278. PMID 18452647.
  13. "Placental Insufficiency". MalaCards.
  14. Regnault, T. R.; Orbus, R. J.; De Vrijer, B.; Davidsen, M. L.; Galan, H. L.; Wilkening, R. B.; Anthony, R. V. (2002). "Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR)". Placenta. 23 (2–3): 132–144. doi:10.1053/plac.2001.0757. PMID 11945079.
  15. "Twin-to-Twin Transfusion Syndrome". MalaCards.

Further reading
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