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Gene Review

FGF2  -  fibroblast growth factor 2 (basic)

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Disease relevance of FGF2


High impact information on FGF2


Chemical compound and disease context of FGF2


Biological context of FGF2

  • Experiments with cells lacking active HS indicated that extended >/=14-mer heparin domains were needed to enhance cell proliferation and Erk phosphorylation by FGF8b, whereas in cells stimulated with FGF1 or FGF2 the corresponding responses were achieved by much shorter, 6-8-mer, oligosaccharides [13].
  • The addition of FGF2 greatly reduced apoptosis over a 7-day culture period [14].
  • Both inhibition of ERK2 activation, which decreased Bcl-xl synthesis, and downregulation of Bcl-x by antisense oligonucleotide treatment inhibited the survival-promoting activity of FGF2 [14].
  • After 4 days of culture, a dramatic and sustained upregulation of FGF1 protein expression occurs specifically in response to exogenous FGF2 [15].
  • In addition several studies demonstrate that exogenous FGF2 can promote retinal cell survival in vitro and in vivo [15].

Anatomical context of FGF2

  • The role of heparin and heparan sulfate in the binding and signaling of fibroblast growth factors (FGFs) has been subject to intense investigation, but the studies have largely been confined to two species (FGF1 and FGF2) of the family with approximately 20 members [13].
  • Both FGF1 and bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2 [14].
  • We demonstrated that specific inhibition of poly(ADP-ribose) polymerase activity via 3-aminobenzamide (3ABA) or NAD+ deprivation prevents FGF2-mediated uPA mRNA over-expression and cell-associated plasminogen activator (PA) production in GM7373 endothelial cell line [16].
  • Therefore, it is suggested that the increase in the number of FGF low affinity receptors present on the cell surface or basement membrane could account for a part of the greater proliferative response of aged RPE cells to FGF2 [17].
  • The aim of this study was to investigate the possible participation of fibroblast growth factor (FGF) family members: FGF1, FGF2, and FGF7, and their receptor variants: FGFR, FGFR2IIIb, and FGFR2IIIc in theca interna (TI) and granulosa cell (GC) compartments of bovine follicles during final growth [18].

Associations of FGF2 with chemical compounds

  • Fibroblast growth factor 1 (FGF1) and 2 (FGF2) bind to two classes of receptors: the high affinity receptors, a family of four known transmembrane tyrosine kinases (FGF R1-R4), and the low affinity receptors, cell surface and basement membrane heparan sulfate proteoglycan (HSPG) [17].
  • Poly(ADP-ribose) polymerase involved in this mechanism is mainly the 60 kDa molecular mass isoform, that presents an increase in serine phosphorylation in the presence of FGF2 [16].
  • We verified that FGF2 stimulates poly(ADP-ribose) polymerase activity by a DNA strand breaks-independent manner which involves a mitogen-activated protein kinases (MAPK)-dependent pathway, as confirmed by using PD98059 inhibitor and anisomycin stimulation [16].
  • Involvement of pro-inflammatory cytokines, mediators of inflammation, and basic fibroblast growth factor in prostaglandin F2alpha-induced luteolysis in bovine corpus luteum [19].
  • A basic fibroblast growth factor (FGF) has been purified to homogeneity from bovine testis, using ammonium sulfate precipitation of the crude extract followed by three chromatographic steps, involving cation-exchange, heparin-Sepharose, and reversed-phase HPLC [20].

Physical interactions of FGF2


Regulatory relationships of FGF2

  • However, the inhibition by TGF beta was greatly enhanced if the cells were pretreated with TGF beta before addition of bFGF [25].
  • FGF-1 stimulated DNA synthesis while FGF-2 in concentrations above 10 ng/ml inhibited DNA synthesis [26].
  • However, the presence of FGF-2 in the medium up-regulated the expression of both VEGF receptors (VEGFR-1 and VEGFR-2), whereas oestradiol or VEGF treatment showed no effect on the expression of these receptors [27].
  • These effects were due to the release of fibroblast growth factor 2 (FGF2) stored in the extracellular matrix but not to direct interactions with FGF receptors since V189 was inefficient on heparan sulfate-deficient cells expressing constitutively FGF-R1 [28].
  • Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells [29].

Other interactions of FGF2

  • By contrast, the saccharide structures required for the biological activity of FGF8b differed significantly from those characteristic for FGF1 and FGF2 [13].
  • A 24 h-pretreatment of cells with bFGF resulted in abolition of the TGF beta 1 inhibitory effect on DNA synthesis [30].
  • Immunohistochemical analysis of bFGF, TGF-beta1 and catalase in rectus abdominis muscle from cattle foetuses at 180 and 260 days post-conception [31].
  • FGF2-mediated upregulation of urokinase-type plasminogen activator expression requires a MAP-kinase dependent activation of poly(ADP-ribose) polymerase [16].
  • In conclusion, the balance between intracellular growth factors (bFGF and TGF-beta1) and the activity of antioxidant enzyme CAT may participate in the regulation of the transition from myoblast proliferation to differentiation [31].

Analytical, diagnostic and therapeutic context of FGF2


  1. Sugar-induced modification of fibroblast growth factor 2 reduces its angiogenic activity in vivo. Facchiano, F., Lentini, A., Fogliano, V., Mancarella, S., Rossi, C., Facchiano, A., Capogrossi, M.C. Am. J. Pathol. (2002) [Pubmed]
  2. Tyrosine kinase receptor activation inhibits NPR-C in lung arterial smooth muscle cells. Sun, J.Z., Oparil, S., Lucchesi, P., Thompson, J.A., Chen, Y.F. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  3. Specific binding of basic fibroblast growth factor to basement membrane-like structures and to purified heparan sulfate proteoglycan of the EHS tumor. Vigny, M., Ollier-Hartmann, M.P., Lavigne, M., Fayein, N., Jeanny, J.C., Laurent, M., Courtois, Y. J. Cell. Physiol. (1988) [Pubmed]
  4. Signalling crosstalk in FGF2-mediated protection of endothelial cells from HIV-gp120. Langford, D., Hurford, R., Hashimoto, M., Digicaylioglu, M., Masliah, E. BMC neuroscience [electronic resource]. (2005) [Pubmed]
  5. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Schweigerer, L., Neufeld, G., Friedman, J., Abraham, J.A., Fiddes, J.C., Gospodarowicz, D. Nature (1987) [Pubmed]
  6. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Abraham, J.A., Mergia, A., Whang, J.L., Tumolo, A., Friedman, J., Hjerrild, K.A., Gospodarowicz, D., Fiddes, J.C. Science (1986) [Pubmed]
  7. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. Benzaquen, L.R., Nicholson-Weller, A., Halperin, J.A. J. Exp. Med. (1994) [Pubmed]
  8. Biophysical characterization, including disulfide bond assignments, of the anti-angiogenic type 1 domains of human thrombospondin-1. Huwiler, K.G., Vestling, M.M., Annis, D.S., Mosher, D.F. Biochemistry (2002) [Pubmed]
  9. Curcumin is an in vivo inhibitor of angiogenesis. Arbiser, J.L., Klauber, N., Rohan, R., van Leeuwen, R., Huang, M.T., Fisher, C., Flynn, E., Byers, H.R. Mol. Med. (1998) [Pubmed]
  10. Tranilast inhibits protein kinase C-dependent signalling pathway linked to angiogenic activities and gene expression of retinal microcapillary endothelial cells. Koyama, S., Takagi, H., Otani, A., Suzuma, K., Nishimura, K., Honda, Y. Br. J. Pharmacol. (1999) [Pubmed]
  11. Inhibition of corneal angiogenesis by local application of vasostatin. Wu, P.C., Yang, L.C., Kuo, H.K., Huang, C.C., Tsai, C.L., Lin, P.R., Wu, P.C., Shin, S.J., Tai, M.H. Mol. Vis. (2005) [Pubmed]
  12. Growth control of A431 cells in protein-free medium: secretory products do not affect cell growth. Masuda, Y., Yoshitake, Y., Nishikawa, K. In Vitro Cell. Dev. Biol. (1988) [Pubmed]
  13. Heparin/Heparan sulfate domains in binding and signaling of fibroblast growth factor 8b. Loo, B.M., Salmivirta, M. J. Biol. Chem. (2002) [Pubmed]
  14. Both FGF1 and bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2. Bryckaert, M., Guillonneau, X., Hecquet, C., Courtois, Y., Mascarelli, F. Oncogene (1999) [Pubmed]
  15. FGF2-stimulated release of endogenous FGF1 is associated with reduced apoptosis in retinal pigmented epithelial cells. Guillonneau, X., Régnier-Ricard, F., Dupuis, C., Courtois, Y., Mascarelli, F. Exp. Cell Res. (1997) [Pubmed]
  16. FGF2-mediated upregulation of urokinase-type plasminogen activator expression requires a MAP-kinase dependent activation of poly(ADP-ribose) polymerase. Caldini, R., Barletta, E., Del Rosso, M., Giovannelli, L., Chevanne, M. J. Cell. Physiol. (2005) [Pubmed]
  17. In vitro changes in plasma membrane heparan sulfate proteoglycans and in perlecan expression participate in the regulation of fibroblast growth factor 2 mitogenic activity. Guillonneau, X., Tassin, J., Berrou, E., Bryckaert, M., Courtois, Y., Mascarelli, F. J. Cell. Physiol. (1996) [Pubmed]
  18. Expression and localization of fibroblast growth factor (FGF) family members during the final growth of bovine ovarian follicles. Berisha, B., Sinowatz, F., Schams, D. Mol. Reprod. Dev. (2004) [Pubmed]
  19. Involvement of pro-inflammatory cytokines, mediators of inflammation, and basic fibroblast growth factor in prostaglandin F2alpha-induced luteolysis in bovine corpus luteum. Neuvians, T.P., Schams, D., Berisha, B., Pfaffl, M.W. Biol. Reprod. (2004) [Pubmed]
  20. Isolation and partial characterization of basic fibroblast growth factor from bovine testis. Ueno, N., Baird, A., Esch, F., Ling, N., Guillemin, R. Mol. Cell. Endocrinol. (1987) [Pubmed]
  21. Transforming growth factor beta 1 and adrenocorticotropin differentially regulate the synthesis of adrenocortical cell heparan sulfate proteoglycans and their binding of basic fibroblast growth factor. Jiang, Z., Savona, C., Chambaz, E.M., Feige, J.J. J. Cell. Physiol. (1992) [Pubmed]
  22. Fibroblast growth factor-2 binds to the regulatory beta subunit of CK2 and directly stimulates CK2 activity toward nucleolin. Bonnet, H., Filhol, O., Truchet, I., Brethenou, P., Cochet, C., Amalric, F., Bouche, G. J. Biol. Chem. (1996) [Pubmed]
  23. Carboxyl-terminal heparin-binding fragments of platelet factor 4 retain the blocking effect on the receptor binding of basic fibroblast growth factor. Sato, Y., Waki, M., Ohno, M., Kuwano, M., Sakata, T. Jpn. J. Cancer Res. (1993) [Pubmed]
  24. Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes. Duraisamy, Y., Slevin, M., Smith, N., Bailey, J., Zweit, J., Smith, C., Ahmed, N., Gaffney, J. Angiogenesis (2001) [Pubmed]
  25. The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells. Saksela, O., Moscatelli, D., Rifkin, D.B. J. Cell Biol. (1987) [Pubmed]
  26. Involvement of growth factors in the regulation of pubertal mammary growth in cattle. Purup, S., Vestergaard, M., Sejrsen, K. Adv. Exp. Med. Biol. (2000) [Pubmed]
  27. Expression pattern of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) system members in bovine corpus luteum endothelial cells during treatment with FGF-2, VEGF or oestradiol. Gabler, C., Plath-Gabler, A., Killian, G.J., Berisha, B., Schams, D. Reprod. Domest. Anim. (2004) [Pubmed]
  28. Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor. Jonca, F., Ortéga, N., Gleizes, P.E., Bertrand, N., Plouët, J. J. Biol. Chem. (1997) [Pubmed]
  29. Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation. Dighiero, P., Behar-Cohen, F., Courtois, Y., Goureau, O. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  30. Basic FGF treatment of endothelial cells down-regulates the 85-KDa TGF beta receptor subtype and decreases the growth inhibitory response to TGF-beta 1. Fafeur, V., Terman, B.I., Blum, J., Böhlen, P. Growth Factors (1990) [Pubmed]
  31. Immunohistochemical analysis of bFGF, TGF-beta1 and catalase in rectus abdominis muscle from cattle foetuses at 180 and 260 days post-conception. Orzechowski, A., Gajkowska, B., Wojewódzka, U., Cassar-Malek, I., Picard, B., Hocquette, J.F. Tissue & cell. (2002) [Pubmed]
  32. Analysis of fibroblast growth factor 2 (FGF2) gene transcription and protein distribution in the bovine testis. Abd-Elmaksoud, A., Vermehren, M., Nützel, F., Habermann, F.A., Sinowatz, F. Growth Factors (2005) [Pubmed]
  33. Basic fibroblast growth factor: expression in cultured bovine vascular smooth muscle cells. Gospodarowicz, D., Ferrara, N., Haaparanta, T., Neufeld, G. Eur. J. Cell Biol. (1988) [Pubmed]
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