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Gene Review

Vegfb  -  vascular endothelial growth factor B

Mus musculus

Synonyms: VEGF-B, VEGF-related factor, VRF, Vascular endothelial growth factor B, Vrf
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Disease relevance of Vegfb


High impact information on Vegfb

  • Conditioned medium from transfected 293EBNA cells expressing VEGF-B stimulated DNA synthesis in endothelial cells [5].
  • RESULTS: In AIA studies, Vegfb(+/+) mice displayed significant knee joint swelling and synovial inflammation 7 days after intraarticular injection of antigen [4].
  • In contrast to VEGF, the isoforms VEGF-B and VEGF-C are poorly regulated by growth and oncogenic factors [6].
  • The two identified isoforms of vascular endothelial growth factor B are generated by alternative splicing where different splice acceptor sites in exon 6 introduce a frameshift and a partial use of different but overlapping reading frames [7].
  • Here we compare the regulation of steady-state levels of VEGF, VEGF-B and VEGF-C mRNAs in cultured cells by a variety of stimuli implicated in angiogenesis and endothelial cell physiology [8].

Chemical compound and disease context of Vegfb

  • CONCLUSION(S): The data confirm that CO2 pneumoperitoneum is a cofactor in adhesion formation and demonstrate that VEGFR-1 plays a role in pneumoperitoneum-enhanced adhesions, which is consistent with a role of placental growth factor, VEGF-A, and VEGF-B in pneumoperitoneum-enhanced adhesions [9].

Biological context of Vegfb


Anatomical context of Vegfb

  • Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies [1].
  • Recent analysis of mice with a targeted deletion of the VEGF-B gene has revealed a defect in heart development and function consistent with an important role in vascularization of the myocardium (Bellomo D et al., 2000, Circ Res 86:E29-E35) [3].
  • Transgenic overexpression of vascular endothelial growth factor-B isoforms by endothelial cells potentiates postnatal vessel growth in vivo and in vitro [14].
  • Proangiogenic effect of VEGF-B was confirmed in a mouse model of surgically induced hindlimb ischemia [11].
  • To determine if VegfB regulates the severity of cerebral ischemia, the middle cerebral artery was occluded in VegfB-knockout, heterozygous, and wild-type mice, and the volume of the resulting cerebral infarcts and associated impairment of neurologic function were measured [15].

Associations of Vegfb with chemical compounds

  • Methods: Retinal vascular growth was measured in Vegfb-/- knockout mice raised under normal conditions, and Vegfb-/- knockout mice with an oxygen-induced proliferative retinopathy [16].
  • Vascular endothelial growth factor-B (VegfB) is an angiogenic protein related to VegfA, although it acts on a different set of tyrosine kinase receptors [15].
  • Intracerebroventricular VEGFB administration increased BrdU incorporation into cells of neuronal lineage both in vitro and in vivo, and VEGFB-KO mice showed impaired neurogenesis, consistent with a neurogenesis-promoting effect of VEGFB [17].
  • When HB2 cells were stimulated by norepinephrine, the VEGF mRNA level increased without a change in that of VEGF-B, while the VEGF-C mRNA level decreased [18].

Regulatory relationships of Vegfb


Other interactions of Vegfb

  • Compared with VEGF-A, relatively little is known about the biological role of the VEGF-R1 specific ligand, VEGF-B [3].
  • Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension [2].
  • In comparison with wild-type mice, basal adhesions were higher in VEGF-A(164/164) mice and similar in VEGF-B(-/-) and PlGF(-/-) mice [20].
  • The effect of VEGF was not reproduced by VEGF-B or placental growth factor, but was blocked by SU1498, consistent with a VEGFR2 receptor-mediated process [21].

Analytical, diagnostic and therapeutic context of Vegfb


  1. Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia. Bellomo, D., Headrick, J.P., Silins, G.U., Paterson, C.A., Thomas, P.S., Gartside, M., Mould, A., Cahill, M.M., Tonks, I.D., Grimmond, S.M., Townson, S., Wells, C., Little, M., Cummings, M.C., Hayward, N.K., Kay, G.F. Circ. Res. (2000) [Pubmed]
  2. Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension. Wanstall, J.C., Gambino, A., Jeffery, T.K., Cahill, M.M., Bellomo, D., Hayward, N.K., Kay, G.F. Cardiovasc. Res. (2002) [Pubmed]
  3. Purification and refolding of vascular endothelial growth factor-B. Scrofani, S.D., Fabri, L.J., Xu, P., Maccarone, P., Nash, A.D. Protein Sci. (2000) [Pubmed]
  4. Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Mould, A.W., Tonks, I.D., Cahill, M.M., Pettit, A.R., Thomas, R., Hayward, N.K., Kay, G.F. Arthritis Rheum. (2003) [Pubmed]
  5. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Olofsson, B., Pajusola, K., Kaipainen, A., von Euler, G., Joukov, V., Saksela, O., Orpana, A., Pettersson, R.F., Alitalo, K., Eriksson, U. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. p42/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. Milanini, J., Viñals, F., Pouysségur, J., Pagès, G. J. Biol. Chem. (1998) [Pubmed]
  7. Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform. Olofsson, B., Pajusola, K., von Euler, G., Chilov, D., Alitalo, K., Eriksson, U. J. Biol. Chem. (1996) [Pubmed]
  8. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Enholm, B., Paavonen, K., Ristimäki, A., Kumar, V., Gunji, Y., Klefstrom, J., Kivinen, L., Laiho, M., Olofsson, B., Joukov, V., Eriksson, U., Alitalo, K. Oncogene (1997) [Pubmed]
  9. Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in mice. Molinas, C.R., Binda, M.M., Carmeliet, P., Koninckx, P.R. Fertil. Steril. (2004) [Pubmed]
  10. Assignment of the mouse Vegfb gene to mouse chromosome 19 B by in situ hybridization. Gerace, L., Cirenei, N., Cappelletti, M., Petraroli, R., Sebastiani, F., Marziliano, N. Cytogenet. Cell Genet. (2001) [Pubmed]
  11. Vascular endothelial growth factor-B promotes in vivo angiogenesis. Silvestre, J.S., Tamarat, R., Ebrahimian, T.G., Le-Roux, A., Clergue, M., Emmanuel, F., Duriez, M., Schwartz, B., Branellec, D., Lévy, B.I. Circ. Res. (2003) [Pubmed]
  12. Extracellular matrix tenascin-X in combination with vascular endothelial growth factor B enhances endothelial cell proliferation. Ikuta, T., Ariga, H., Matsumoto, K. Genes Cells (2000) [Pubmed]
  13. Analysis of the promoter region of the human VEGF-related factor gene. Silins, G., Grimmond, S., Egerton, M., Hayward, N. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  14. Transgenic overexpression of vascular endothelial growth factor-B isoforms by endothelial cells potentiates postnatal vessel growth in vivo and in vitro. Mould, A.W., Greco, S.A., Cahill, M.M., Tonks, I.D., Bellomo, D., Patterson, C., Zournazi, A., Nash, A., Scotney, P., Hayward, N.K., Kay, G.F. Circ. Res. (2005) [Pubmed]
  15. Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice. Sun, Y., Jin, K., Childs, J.T., Xie, L., Mao, X.O., Greenberg, D.A. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  16. Vascular endothelial growth factor-B and retinal vascular development in the mouse. Reichelt, M., Shi, S., Hayes, M., Kay, G., Batch, J., Gole, G.A., Browning, J. Clin. Experiment. Ophthalmol. (2003) [Pubmed]
  17. Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: evidence from knockout mice and growth factor administration. Sun, Y., Jin, K., Childs, J.T., Xie, L., Mao, X.O., Greenberg, D.A. Dev. Biol. (2006) [Pubmed]
  18. Isoform-specific regulation of vascular endothelial growth factor (VEGF) family mRNA expression in cultured mouse brown adipocytes. Asano, A., Irie, Y., Saito, M. Mol. Cell. Endocrinol. (2001) [Pubmed]
  19. Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect. Aase, K., von Euler, G., Li, X., Pontén, A., Thorén, P., Cao, R., Cao, Y., Olofsson, B., Gebre-Medhin, S., Pekny, M., Alitalo, K., Betsholtz, C., Eriksson, U. Circulation (2001) [Pubmed]
  20. 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]
  21. Vascular endothelial growth factor stimulates neurite outgrowth from cerebral cortical neurons via Rho kinase signaling. Jin, K., Mao, X.O., Greenberg, D.A. J. Neurobiol. (2006) [Pubmed]
  22. Localization of VEGF-B in the mouse embryo suggests a paracrine role of the growth factor in the developing vasculature. Aase, K., Lymboussaki, A., Kaipainen, A., Olofsson, B., Alitalo, K., Eriksson, U. Dev. Dyn. (1999) [Pubmed]
  23. Differentiation of intracranial morphine self-administration behavior among five brain regions in mice. David, V., Cazala, P. Pharmacol. Biochem. Behav. (1994) [Pubmed]
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