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Gene Review

Pgf  -  placental growth factor

Mus musculus

Synonyms: AI854365, PIGF, PLGF, PlGF, Placenta growth factor, ...
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Disease relevance of Pgf


High impact information on Pgf

  • Placental growth factor (PlGF), which signals through VEGFR1, restored early and late phases of hematopoiesis following BM suppression [5].
  • The late phase of hematopoietic recovery was driven by PlGF-induced upregulation of matrix metalloproteinase-9, mediating the release of soluble Kit ligand [5].
  • By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders [1].
  • The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine [1].
  • Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells [1].

Biological context of Pgf

  • Recent gene inactivation studies in mice have demonstrated that loss of PlGF does not affect development, reproduction, or normal postnatal life [6].
  • Thus, PlGF promotes recruitment of VEGFR1(+) HSCs from a quiescent to a proliferative BM microenvironment, favoring differentiation, mobilization and reconstitution of hematopoiesis [5].
  • These results demonstrate that a single Ig-like domain is the major determinant for VEGF-PlGF interaction and that binding to this domain may initiate a signal transduction cascade [7].
  • We combined real-time PCR of endometrium from nonpregnant and gestation day (gd)6-18 C57BL6/J (B6) mice with immunohistology to analyze PlGF expression in normal mouse pregnancy [3].
  • Thus, in mice, PlGF plays an important role in successful uNK cell proliferation and/or differentiation [3].

Anatomical context of Pgf

  • Placental growth factor is a survival factor for tumor endothelial cells and macrophages [8].
  • To estimate the significance of uNK cell-derived PlGF, PlGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 null/common gamma chain null mice and in laser capture-microdissected B6 uNK cells [3].
  • PlGF overexpression results in a substantial increase in the number, branching and size of dermal blood vessels as well as in enhanced vascular permeability [9].
  • Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood [9].
  • Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation [9].

Associations of Pgf with chemical compounds


Other interactions of Pgf

  • Furthermore, transfected cells expressing these chimeric Flt-4 receptors exhibited increased DNA synthesis in response to VEGF or PlGF [7].
  • The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF [9].
  • Neutralization of VEGF-A caused a significant reduction in the hyaloid and retinal vasculature, whereas PlGF antibody treatment caused a marked persistence of the hyaloid without significantly affecting retinal vascular development [12].
  • We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice [13].
  • To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette [9].

Analytical, diagnostic and therapeutic context of Pgf

  • Addition of PlGF to in vitro kidney organ cultures stimulates branching of the ureteric bud [14].
  • The localization of VEGF-A and PlGF in the retina, as revealed by in situ hybridization and immunohistochemistry, was also similar [12].
  • RESULTS: Quantitative (real-time) reverse transcription-polymerase chain reaction (RT-PCR) demonstrated similar expression patterns of VEGF-A and PlGF mRNA during neonatal retinal development, although the fluctuation between time periods was greater overall for VEGF-A [12].
  • OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in adhesion formation after laparoscopic surgery [15].
  • Finally, we have mapped the mouse Plgf gene to Chr 12, one cM from D12Mit5, and the human PlGF gene to 14q24, using both FISH and genetic crosses [16].


  1. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Carmeliet, P., Moons, L., Luttun, A., Vincenti, V., Compernolle, V., De Mol, M., Wu, Y., Bono, F., Devy, L., Beck, H., Scholz, D., Acker, T., DiPalma, T., Dewerchin, M., Noel, A., Stalmans, I., Barra, A., Blacher, S., Vandendriessche, T., Ponten, A., Eriksson, U., Plate, K.H., Foidart, J.M., Schaper, W., Charnock-Jones, D.S., Hicklin, D.J., Herbert, J.M., Collen, D., Persico, M.G. Nat. Med. (2001) [Pubmed]
  2. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. Yano, K., Liaw, P.C., Mullington, J.M., Shih, S.C., Okada, H., Bodyak, N., Kang, P.M., Toltl, L., Belikoff, B., Buras, J., Simms, B.T., Mizgerd, J.P., Carmeliet, P., Karumanchi, S.A., Aird, W.C. J. Exp. Med. (2006) [Pubmed]
  3. Genetic deletion of placenta growth factor in mice alters uterine NK cells. Tayade, C., Hilchie, D., He, H., Fang, Y., Moons, L., Carmeliet, P., Foster, R.A., Croy, B.A. J. Immunol. (2007) [Pubmed]
  4. Loss of placental growth factor protects mice against vascular permeability in pathological conditions. Luttun, A., Brusselmans, K., Fukao, H., Tjwa, M., Ueshima, S., Herbert, J.M., Matsuo, O., Collen, D., Carmeliet, P., Moons, L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  5. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Hattori, K., Heissig, B., Wu, Y., Dias, S., Tejada, R., Ferris, B., Hicklin, D.J., Zhu, Z., Bohlen, P., Witte, L., Hendrikx, J., Hackett, N.R., Crystal, R.G., Moore, M.A., Werb, Z., Lyden, D., Rafii, S. Nat. Med. (2002) [Pubmed]
  6. Structure and function of placental growth factor. De Falco, S., Gigante, B., Persico, M.G. Trends Cardiovasc. Med. (2002) [Pubmed]
  7. The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade. Davis-Smyth, T., Chen, H., Park, J., Presta, L.G., Ferrara, N. EMBO J. (1996) [Pubmed]
  8. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Adini, A., Kornaga, T., Firoozbakht, F., Benjamin, L.E. Cancer Res. (2002) [Pubmed]
  9. Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability. Odorisio, T., Schietroma, C., Zaccaria, M.L., Cianfarani, F., Tiveron, C., Tatangelo, L., Failla, C.M., Zambruno, G. J. Cell. Sci. (2002) [Pubmed]
  10. VEGFR-1-selective VEGF homologue PlGF is arteriogenic: evidence for a monocyte-mediated mechanism. Pipp, F., Heil, M., Issbrücker, K., Ziegelhoeffer, T., Martin, S., van den Heuvel, J., Weich, H., Fernandez, B., Golomb, G., Carmeliet, P., Schaper, W., Clauss, M. Circ. Res. (2003) [Pubmed]
  11. Expression of the VEGF gene family during retinal vaso-obliteration and hypoxia. Simpson, D.A., Murphy, G.M., Bhaduri, T., Gardiner, T.A., Archer, D.B., Stitt, A.W. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  12. Role of vascular endothelial growth factor and placental growth factors during retinal vascular development and hyaloid regression. Feeney, S.A., Simpson, D.A., Gardiner, T.A., Boyle, C., Jamison, P., Stitt, A.W. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  13. Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation. Khurana, R., Moons, L., Shafi, S., Luttun, A., Collen, D., Martin, J.F., Carmeliet, P., Zachary, I.C. Circulation (2005) [Pubmed]
  14. Transcriptional activation of placental growth factor by the forkhead/winged helix transcription factor FoxD1. Zhang, H., Palmer, R., Gao, X., Kreidberg, J., Gerald, W., Hsiao, L., Jensen, R.V., Gullans, S.R., Haber, D.A. Curr. Biol. (2003) [Pubmed]
  15. Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice. Molinas, C.R., Campo, R., Dewerchin, M., Eriksson, U., Carmeliet, P., Koninckx, P.R. Fertil. Steril. (2003) [Pubmed]
  16. The placenta growth factor gene of the mouse. DiPalma, T., Tucci, M., Russo, G., Maglione, D., Lago, C.T., Romano, A., Saccone, S., Della Valle, G., De Gregorio, L., Dragani, T.A., Viglietto, G., Persico, M.G. Mamm. Genome (1996) [Pubmed]
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