[en] Placental growth factor (PlGF) is an angiogenic factor that belongs to the vascular endothelial growth factor (VEGF) family. Besides its well known capacity to potentiate the angiogenic action of VEGF, PlGF also participates in inflammatory processes by attracting and activating monocytes; it plays therefore more specifically a role in pathological conditions. PIGF and its two receptors, VEGFR-1 and neuropilins (NRPs), are expressed in the brain and increase after experimental stroke, but their precise functions in the nervous system remain underexplored. In this review article, we summarize present knowledge on the role of PlGF in various nervous system disease processes. Given the available data, P1GF has neuroprotective and neurotrophic properties that make it an actor of considerable interest in the pathophysiology and potentially in the therapy of degenerative and traumatic brain or spinal cord diseases.
Disciplines :
Neurosciences & behavior
Author, co-author :
Chaballe, Linda ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Schoenen, Jean ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Franzen, Rachelle ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Language :
English
Title :
Placental growth factor: a tissue modelling factor with therapeutic potentials in neurology?
Vesalius A. De Humani Corporis Fabrica (The Fabric of the Human Body). Oporinus, Basel, 1543.
Martin P, Lewis J. Origins of the neurovascular bundle: interactions between developing nerves and blood vessels in embryonic chick skin. Int. J. Dev. Biol. 1989; 33: 379-387.
Neufeld G, Cohen T, Shraga N, Lange T, Kessler O, Herzog Y. The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis. Trends Cardiovasc Med. 2002; 12: 13-19.
Carmeliet P. Blood vessels and nerves: common signals, pathways and diseases. Nature Rev. Genet. 2003; 4: 710-720.
Gu C, Rodriguez ER, Reimert DV, Shu T, Fritzsch B. et al. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell. 2003; 5: 45-57.
Autiero M, De Smet F, Claes F, Carmeliet P. Role of neural guidance signals in blood vessel navigation. Cardiovasc Res. 2005; 65: 629-638.
Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature. 2005; 436: 193-200.
Fantin A, Maden CH, Ruhrberg C. Neuropilin ligands in vascular and neuronal patterning. Biochem Soc Trans. 2009; 37: 1228-32.
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983; 219: 983-985.
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246: 1306-1309.
Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998; 92: 735-45.
Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF 165. J Biol Chem. 2000; 275: 18040-5. Erratum in: J Biol Chem. 2000; 275: 29922.
Bagnard D, Vaillant C, Khuth ST, Dufay N, Lohrum M. et al. Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor. J Neurosci. 2001; 21: 3332-3341.
Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA. 2002; 99: 11946-11950.
Tjwa M, Luttun A, Autiero M, Carmeliet P. VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res. 2003; 314: 5-14.
Zhu Y, Jin K, Mao XO, Greenberg DA. Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression. FASEB J. 2003; 17: 186-193.
Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S. et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nature Neurosci. 2006; 9: 340-348.
Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D. et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet. 2001; 28: 131-138.
Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F. et al. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet. 2003; 34: 383-94.
Li B, Xu W, Luo C, Gozal D, Liu R. VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SoD1-mediated motor neuron cell death. Brain Res Mol Brain Res. 2003; 111: 155-64.
Devos D, Moreau C, Lassalle P, Perez T, De Seze J. et al. Low levels of the vascular endothelial growth factor in CSF from early ALS patients. Neurology. 2004; 62: 2127-9.
Van Den Bosch L, Storkebaum E, Vleminckx V, Moons L, Vanopdenbosch L. et al. Effects of vascular endothelial growth factor (VEGF) on motor neuron degeneration. Neurobiol Dis. 2004; 17: 21-28.
Zheng C, Nennesmo I, Fadeel B, Henter JI. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol. 2004; 56: 564-7.
Wang Y, Mao XO, Xie L, Banwait S, Marti HH, Greenberg DA, Jin K. Vascular endothelial growth factor overexpression delays neurodegeneration and prolongs survival in amyotrophic lateral sclerosis mice. J Neurosci. 2007; 27: 304-7.
Chen D, Shen L, Wang L, Lu A, Zhang H. et al. Association of polymorphisms in vascular endothelial growth factor gene with the age of onset of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2007; 8: 144-9.
Zheng C, Sköld MK, Li J, Nennesmo I, Fadeel B, Henter JI. VEGF reduces astrogliosis and preserves neuromuscular junctions in ALS transgenic mice. Biochem Biophys Res Commun. 2007; 363: 989-93.
Hwang DH, Lee HJ, Park IH, Seok JI, Kim BG, Joo IS, Kim SU. Intrathecal transplantation of human neural stem cells overexpressing VEGF provides behavioral improvement, disease onset delay and survival extension in transgenic ALS mice. Gene Ther. 2009; 16: 1234-44.
Lunn JS, Sakowski SA, Kim B, Rosenberg AA, Feldman EL. Vascular endothelial growth factor prevents G93A-SoD1-induced motor neuron degeneration. Dev Neurobiol. 2009; 69: 871-84.
Kalaria RN, Cohen DL, Premkumar DR, Nag S, LaManna JC, Lust WD. Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. Brain Res. 1998; 62: 101-105.
Mateo I, Llorca J, Infante J, Rodriguez-Rodriguez E, Fernandez-Viadero C. et al. Low serum VEGF levels are associated with Alzheimer's disease. Acta Neurol Scand. 2007; 116: 56-58.
Ryu JK, Cho T, Choi HB, Wang YT, McLarnon JG. Microglial VEGF receptor response is an integral chemotactic component in Alzheimer's disease pathology. J Neurosci. 2009; 29: 3-13.
Yasuhara T, Shingo T, Muraoka K, Wen Ji Y, Kameda M. et al. The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model. Brain Res. 2005; 1038: 1-10.
Tian YY, Tang CJ, Wang JN, Feng Y, Chen XW. et al. Favorable effects of VEGF gene transfer on a rat model of Parkinson disease using adeno-associated viral vectors. Neurosci Lett. 2007; 421: 239-44.
Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K. et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000; 106: 829-38.
Yang ZJ, Bao WL, Qiu MH, Zhang LM, Lu SD, Huang YL, Sun FY. Role of vascular endothelial growth factor in neuronal DNA damage and repair in rat brain following a transient cerebral ischemia. J Neurosci Res. 2002; 70: 140-9.
Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003; 111: 1843-51.
Manoonkitiwongsa PS, Schultz RL, McCreery DB, Whitter EF, Lyden PD Neuroprotection of ischemic brain by vascular endothelial growth factor is critically dependent on proper dosage and may be compromised by angiogenesis. J Cereb Blood Flow Metab. 2004; 24: 693-702.
Chu K, Park KI, Lee ST, Jung KH, Ko SY. et al. Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia. Neurosci Res. 2005; 53: 384-90.
Wang Y, Galvan V, Gorostiza O, Ataie M, Jin K, Greenberg DA. Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat. Brain Res. 2006; 1115: 186-93.
Hermann DM, Zechariah A. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. J Cereb Blood Flow Metab. 2009; 29: 1620-43.
Wang YQ, Cui HR, Yang SZ, Sun HP, Qiu MH, Feng XY, Sun FY. VEGF enhance cortical newborn neurons and their neurite development in adult rat brain after cerebral ischemia. Neurochem Int. 2009; 55: 629-36.
Emerich DF, Silva E, Ali O, Mooney D, Bell W. et al. Injectable VEGF hydrogels produce near complete neurological and anatomical protection following cerebral ischemia in rats. Cell Transplant. 2010 Apr 21.
Facchiano F, Fernandez E, Mancarella S, Maira G, Miscusi M. et al. Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor. J Neurosurg. 2002; 97: 161-8.
Liu Y, Figley S, Spratt SK, Lee G, Ando D. et al. An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury. Neurobiol Dis. 2010; 37: 384-93.
Kim HM, Hwang DH, Lee JE, Kim SU, Kim BG. Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. PLoS One. 2009; 4: e4987.
Maglione D, Guerriero V, Viglietto G, Delli Bovi P, Persico MG. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA. 1991; 88: 9267-9271.
De Falco S, Gigante B, Persico MG, Structure and function of Placental growth factor. Trends Cardiovasc. Med. 2002; 12: 241-6.
Yonekura H, Sakurai S, Liu X, Migita H, Wang H, Yamagishi S-I et al. Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. J Biol Chem. 1999; 274: 35172-8.
Beck H, Acker T, Puschel AW, Fujisawa H, Carmeliet P, Plate KH. Cell type-specific expression of neuropilins in an MCA-occlusion model in mice suggests a potential role in post-ischemic brain remodelling. J Neuropathol Exp Neurol. 2002; 61: 339-50.
Autiero M, Luttun A, Tjwa M, Carmeliet P, Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost. 2003; 1: 1356-70.
Clauss M, Weich H, Breier G, Knies U, Röckl W, Waltenberger J, Risau W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem. 1996; 271: 17629-34.
Selvaraj SK, Giri RK, Perelman N, Johnson C, Malik P, Kalra VK. Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor. Blood 2003; 102: 1515-24.
Perelman N, Selvaraj SK, Batra S, Luck LR, Erdreich-Epstein A, Coates TD et al. Placenta growth factor activates monocytes and correlates with sickle cell disease severity. Blood 2003; 102: 1506-14.
Storkebaum E, Lambrechts D, Carmeliet P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 2004; 26: 943-54.
Góra-Kupilas K, Jośko J. The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol. 2005; 43: 31-9.
Sun FY, Guo X. Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor. J Neurosci Res. 2005; 79: 180-4.
Hansen TM, Moss AJ, Brindle NP. Vascular endothelial growth factor and angiopoietins in neurovascular regeneration and protection following stroke. Curr Neurovasc Res. 2008; 5: 236-45.
Pucci S, Mazzarelli P, Missiroli F, Regine F, Ricci F. Neuroprotection: VEGF, IL-6, and clusterin: the dark side of the moon. Prog Brain Res. 2008; 173: 555-73.
Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y. et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell. 1999; 99: 59-69.
Migdal M, Huppertz B, Tessler S, Comforti A, Shibuya M. et al. Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem. 1998; 273: 22272-8.
Neufeld G, Kessler O, Herzog Y. The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF. Adv Exp Med Biol. 2002; 515: 81-90.
Hayashi T, Noshita N, Sugawara T, Chan PH. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab. 2003; 23: 166-80.
Cheng L, Jia H, Löhr M, Bagherzadeh A, Holmes DI, Selwood D, Zachary I. Anti-chemorepulsive effects of vascular endothelial growth factor and placental growth factor-2 in dorsal root ganglion neurons are mediated via neuropilin-1 and cyclooxygenasederived prostanoid production. J Biol Chem. 2004; 279: 30654-61.
Du H, Li P, Pan Y, Li W, Hou J. et al. Vascular endothelial growth factor signaling implicated in neuroprotective effects of placental growth factor in an in vitro ischemic model. Brain Res. 2010; 1357: 1-8.
Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci. 2001; 189: 49-57.
Iihoshi S, Honmou O, Houkin K, Hashi K, Kocsis JD. A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats. Brain Res. 2004; 1007: 1-9.
Honma T, Honmou O, Iihoshi S, Harada K, Houkin K. et al. Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol. 2006; 199: 56-66.
van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Regeneration of the ischemic brain by engineered stem cells: fuelling endogenous repair processes. Brain Res Rev. 2009; 61: 1-13.
Chen X, Li Y, Wang L, Katakowski M, Zhang L. et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology. 2002; 22: 275-9.
Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW. et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004; 109: 1543-9.
Liu H, Honmou O, Harada K, Nakamura K, Houkin K, Hamada H, Kocsis JD Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain. 2006; 129: 2734-2745.
Stichel C, Müller HW. The CNS lesion scar: new vistas on an old regeneration barrier, Cell Tissue Res. 1998; 294: 1-9.
Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009; 32: 638-47.
Mani N, Khaibullina A, Krum JM, Rosenstein JM. Astrocyte growth effects of vascular endothelial growth factor (VEGF) application to perinatal neocortical explants: receptor mediation and signal transduction pathways. Exp Neurol. 2005; 192: 394-406.
Krum JM, Mani N, Rosenstein JM. Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury. Exp Neurol. 2008; 212: 108-17.
Mani N, Khaibullina A, Krum JM, Rosenstein JM. Vascular endothelial growth factor enhances migration of astroglial cells in subventricular zone neurosphere cultures. J Neurosci Res. 2010; 88: 248-57.
Beck H, Semisch M, Culmsee C, Plesnila N, Hatzopoulos AK. Egr-1 regulates expression of the glial scar component phosphacan in astrocytes after experimental stroke. Am J Pathol. 2008; 173: 77-92.
Patel N, Kalra VK. Placenta growth factor (PlGF) induced early growth response 1 (Egr-1) regulates hypoxia inducible factor-1{alpha} (HIF-1{alpha}) in endothelial cells. J Biol Chem. 2010; 285: 20570-9.
Scarlato M, Ara J, Bannerman P, Scherer S, Pleasure D. Induction of neuropilins-1 and-2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system. Exp Neurol. 2003; 183: 489-98. Erratum in: Exp Neurol. 2004; 187: 539.
Gupta R, Gray M, Chao T, Bear D, Modafferi E, Mozaffar T. Schwann cells upregulate vascular endothelial growth factor secondary to chronic nerve compression injury. Muscle Nerve. 2005; 31: 452-60.
Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci. 1999a; 19: 5731-40.
Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts. Brain Res. 1999b; 846: 219-28.
Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2000; 197: 591-605.
Chaballe L, Close P, Sempels M, Delstanche S, Fanielle J. et al. Involvement of Placental growth factor in Wallerian degeneration. Glia. 2011; 59: 379-396.
van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L. et al. VEGF antagonism reduces edema formation and tissue damage after ischemia/ reperfusion injury in the mouse brain. J Clin Invest. 1999; 104: 1613-20.
Hillman NJ, Whittles CE, Pocock TM, Williams B, Bates DO. Differential effects of vascular endothelial growth factor-C and placental growth factor-1 on the hydraulic conductivity of frog mesenteric capillaries. J Vasc Res. 2001; 38: 176-86.
Brkovic A, Sirois MG. Vascular permeability induced by VEGF family members in vivo: role of endogenous PAF and NO synthesis. J Cell Biochem. 2007; 100: 727-37.
Luttun A, Brusselmans K, Fukao H, Tjwa M, Ueshima S. et al. Loss of placental growth factor protects mice against vascular permeability in pathological conditions. Biochem Biophys Res Commun. 2002; 295: 428-34.
Odorisio T, Schietroma C, Zaccaria ML, Cianfarani F, Tiveron C. et al. Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability. J Cell Sci. 2002; 115: 2559-67.
Oura H, Bertoncini J, Velasco P, Brown LF, Carmeliet P, Detmar M. A critical role of placental growth factor in the induction of inflammation and edema formation. Blood. 2003; 101: 560-7.
Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V. et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001; 7: 575-83.