Biology:Placental growth factor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Placental growth factor (PlGF) is a protein that in humans is encoded by the PGF gene.[1][2]

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.[3]

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.[4] 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. [5] [6]

Clinical significance

Placental growth factor-expression within human atherosclerotic lesions is associated with plaque inflammation and neovascular growth.[7][8]

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.[9] Alterations in the PGF and the PGF receptor mRNA expression prevent the normal development of placental vasculature.[10]

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.[11]

References

  1. ↑ "Entrez Gene: PGF placental growth factor, vascular endothelial growth factor-related protein". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5228. 
  2. ↑ "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. April 1993. PMID 7681160. 
  3. ↑ Lumbiganon, Pisake, ed (July 2008). "Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders". PLOS ONE 3 (7): e2766. doi:10.1371/journal.pone.0002766. PMID 18648513. Bibcode: 2008PLoSO...3.2766K. 
  4. ↑ Carlson, Bruce (2009). Human Embryology and Developmental Biology. Elsevier. ISBN 978-0-323-05385-3. 
  5. ↑ "UniProtKB - P49763 (PLGF_HUMAN)". https://www.uniprot.org/uniprot/P49763. 
  6. ↑ "Placental Growth Factor". https://www.omim.org/entry/601121. 
  7. ↑ "Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation". Circulation 111 (21): 2828–36. May 2005. doi:10.1161/CIRCULATIONAHA.104.495887. PMID 15911697. http://discovery.ucl.ac.uk/8151/1/8151.pdf. 
  8. ↑ "Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis". BMB Reports 41 (4): 278–86. April 2008. doi:10.5483/BMBRep.2008.41.4.278. PMID 18452647. 
  9. ↑ "Placental Insufficiency". https://www.malacards.org/card/placental_insufficiency. 
  10. ↑ 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. 
  11. ↑ "Twin-to-Twin Transfusion Syndrome". https://www.malacards.org/card/twin_to_twin_transfusion_syndrome. 

Further reading

  • "The discovery of placenta growth factor and its biological activity". Experimental & Molecular Medicine 44 (1): 1–9. January 2012. doi:10.3858/emm.2012.44.1.025. PMID 22228176. 
  • "Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders". Annals of the New York Academy of Sciences 979: 80–93. December 2002. doi:10.1111/j.1749-6632.2002.tb04870.x. PMID 12543719. 
  • "Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor". Proceedings of the National Academy of Sciences of the United States of America 88 (20): 9267–71. October 1991. doi:10.1073/pnas.88.20.9267. PMID 1924389. Bibcode: 1991PNAS...88.9267M. 
  • "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. April 1993. PMID 7681160. 
  • "Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR". The Journal of Biological Chemistry 269 (41): 25646–54. October 1994. doi:10.1016/S0021-9258(18)47298-5. PMID 7929268. 
  • "A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta". Growth Factors 9 (4): 259–68. 1994. doi:10.3109/08977199308991586. PMID 8148155. 
  • "Assignment of vascular endothelial growth factor (VEGF) and placenta growth factor (PLGF) genes to human chromosome 6p12-p21 and 14q24-q31 regions, respectively". Genomics 32 (1): 168–9. February 1996. doi:10.1006/geno.1996.0098. PMID 8786112. 
  • "Placenta growth factor-1 is chemotactic, mitogenic, and angiogenic". Laboratory Investigation; A Journal of Technical Methods and Pathology 76 (4): 517–31. April 1997. PMID 9111514. 
  • "Expression of vascular endothelial growth factor and placenta growth factor in human placenta". Biology of Reproduction 56 (2): 489–94. February 1997. doi:10.1095/biolreprod56.2.489. PMID 9116151. 
  • "Placenta growth factor: identification and characterization of a novel isoform generated by RNA alternative splicing". Biochemical and Biophysical Research Communications 235 (3): 493–8. June 1997. doi:10.1006/bbrc.1997.6813. PMID 9207183. 
  • "Mapping the charged residues in the second immunoglobulin-like domain of the vascular endothelial growth factor/placenta growth factor receptor Flt-1 required for binding and structural stability". The Journal of Biological Chemistry 273 (6): 3216–22. February 1998. doi:10.1074/jbc.273.6.3216. PMID 9452434. 
  • "Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1". Oncogene 16 (3): 359–67. January 1998. doi:10.1038/sj.onc.1201545. PMID 9467961. 
  • "Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]". The Journal of Biological Chemistry 275 (24): 18040–5. June 2000. doi:10.1074/jbc.M909259199. PMID 10748121. 
  • "A sequence-ready physical map of the region containing the human natural killer gene complex on chromosome 12p12.3-p13.2". Genomics 65 (2): 129–36. April 2000. doi:10.1006/geno.2000.6163. PMID 10783260. 
  • "Recombinant production of PIGF-1 and its activity in animal models". Farmaco 55 (3): 165–7. March 2000. doi:10.1016/S0014-827X(00)00012-4. PMID 10919072. 
  • "Angiogenic growth factors in human dentine matrix". Archives of Oral Biology 45 (11): 1013–6. November 2000. doi:10.1016/S0003-9969(00)00075-3. PMID 11000388. 
  • "The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution". The Journal of Biological Chemistry 276 (15): 12153–61. April 2001. doi:10.1074/jbc.M008055200. PMID 11069911. 
  • "Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells". The Journal of Clinical Endocrinology and Metabolism 86 (4): 1823–34. April 2001. doi:10.1210/jcem.86.4.7418. PMID 11297624. 
  • "Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome". Prenatal Diagnosis 22 (1): 8–12. January 2002. doi:10.1002/pd.218. PMID 11810642. 
  • "Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor". Growth Factors 19 (3): 193–206. 2002. doi:10.3109/08977190109001086. PMID 11811792. 
  • "Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain". The Journal of Biological Chemistry 277 (27): 24818–25. July 2002. doi:10.1074/jbc.M200730200. PMID 11986311. 



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