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PGF
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1FZV, 1RV6
Identifiers
Aliases	PGF, D12S1900, PGFL, PLGF, PlGF-2, SHGC-10760, Placental growth factor, PIGF
External IDs	OMIM: 601121; MGI: 105095; HomoloGene: 1978; GeneCards: PGF; OMA:PGF - orthologs
Gene location (Human)
Chr.	Chromosome 14 (human)
End	74,955,626 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	85,224,564 bp
RNA expression pattern
	Top expressed in
	renal medulla; ; cardia; ; pylorus; ; nipple; ; ventral tegmental area; ; trigeminal ganglion; ; inferior ganglion of vagus nerve; ; external globus pallidus; ; superior surface of tongue; ; pars reticulata;
	Top expressed in
	decidua; ; external carotid artery; ; ankle joint; ; internal carotid artery; ; facial motor nucleus; ; embryo; ; saccule; ; lens; ; Smooth muscle tissue of renal pelvis; ; islet of Langerhans;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	heparin binding; protein homodimerization activity; protein binding; protein heterodimerization activity; growth factor activity; vascular endothelial growth factor receptor binding; chemoattractant activity; vascular endothelial growth factor receptor 3 binding;
Cellular component	membrane; extracellular region; extracellular space;
Biological process	cell differentiation; female pregnancy; cell-cell signaling; regulation of morphogenesis of a branching structure; sprouting angiogenesis; multicellular organism development; branching involved in ureteric bud morphogenesis; cellular response to hormone stimulus; animal organ regeneration; positive regulation of cell population proliferation; positive regulation of cell division; signal transduction; angiogenesis; response to hypoxia; positive regulation of endothelial cell proliferation; positive regulation of angiogenesis; vascular endothelial growth factor receptor signaling pathway; induction of positive chemotaxis; positive regulation of mast cell chemotaxis; regulation of signaling receptor activity; positive regulation of protein phosphorylation; vascular endothelial growth factor signaling pathway; positive chemotaxis;
	Sources:Amigo / QuickGO
Orthologs
	5228
	18654
	ENSG00000119630
	ENSMUSG00000004791
	P49763
	P49764
	NM_002632; NM_001207012; NM_001293643
	NM_001271705; NM_008827
	NP_001193941; NP_001280572; NP_002623
	NP_001258634; NP_032853
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000119630 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004791 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: PGF placental growth factor, vascular endothelial growth factor-related protein".
^ 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.
^ 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.
^ Carlson, Bruce (2009). Human Embryology and Developmental Biology. Elsevier. ISBN 978-0-323-05385-3.
^ "UniProtKB - P49763 (PLGF_HUMAN)". UniProt.
^ "Placental Growth Factor". Online Mendelian Inheritance in Man.
^ 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.
^ 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.
^ "Placental Insufficiency". MalaCards.
^ 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.
^ "Twin-to-Twin Transfusion Syndrome". MalaCards.

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