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Fgf2  -  fibroblast growth factor 2

Rattus norvegicus

Synonyms: Basic fibroblast growth factor, FGF-2, Fgf-2, Fibroblast growth factor 2, HBGF-2, ...
 
 
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Disease relevance of Fgf2

  • Given that we have also recently derived from the SHR a rat strain that develops spontaneous cardiac hypertrophy in the absence of hypertension (the Hypertrophic Heart Rat; HHR), we also took the opportunity to examine the sequence of its Fgf2 promoter and coding region [1].
  • Thus, we conclude that variations in the nucleotide sequence of the promoter and coding region of the SHR Fgf2 gene do not play a role in the cardiac hypertrophy of the SHR and HHR strains [1].
  • In a screen of five human glioma cell lines, U118 and U251 cell HSPGs activated FGF-2 signaling via FGFR1c [2].
  • This study unequivocally demonstrates coordinate up-regulation and trafficking of FGF-2 and full-length FGFR1 to the nucleus of reactive astrocytes in an in vivo model of brain injury, thereby implicating a role in nuclear activity for these molecules [3].
  • Within hours after experimental retinal detachment or focal injury, there is a twofold increase in FGFR1 immunoreactivity in the outer nuclear layer that persists for at least 7 days; a similar increase in bFGF immunoreactivity in the interphotoreceptor matrix is also apparent [4].
 

Psychiatry related information on Fgf2

 

High impact information on Fgf2

 

Chemical compound and disease context of Fgf2

 

Biological context of Fgf2

 

Anatomical context of Fgf2

  • In freshly isolated adult rat cardiac myocytes, bFGF mRNA was not detectable by in situ hybridization, although the cells contained significant amounts of bFGF and aFGF as quantified by radioimmunoassays, mitogen assays with immunoneutralization, and Western blotting [21].
  • The addition of bFGF or aFGF in serum-free medium to pure populations of myocytes (after 10 days in culture, at which time they are spread, beating, and multinucleated) led to increased thymidine incorporation [21].
  • These findings strongly suggest that increases in endogenous bFGF and/or CNTF play key roles in injury-induced photoreceptor rescue [22].
  • The direct comparison of U251 glioma cells with normal astrocyte HSPGs demonstrated that the glioma HSPGs had a significantly elevated ability to promote FGF-2-dependent mitogenic signaling via FGFR1c [2].
  • Quantitation of [(35)S]sulfate-labeled proteoglycan and total glycosaminoglycan release from fibroblast matrices indicated that elastase treatment released sulfated proteoglycan from the cell surface in a time- and dose-dependent fashion that correlated strongly with elastase-mediated bFGF release [23].
 

Associations of Fgf2 with chemical compounds

 

Physical interactions of Fgf2

  • These findings reinforce the possibility that IGF-I and/or its receptors and binding proteins are involved in the trophic effects of bFGF on developing brain cells [26].
  • Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells [27].
  • Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor [28].
  • Similarly, rat MG160 subjected to deglycosylation by peptide:N-glycosidase F (PNGase) bound 125I bFGF [29].
  • Visualization of basic fibroblast growth factor binding sites by means of a tissue slice overlay assay also revealed colocalization with glypican [30].
 

Enzymatic interactions of Fgf2

 

Co-localisations of Fgf2

 

Regulatory relationships of Fgf2

 

Other interactions of Fgf2

  • In contrast, no major changes in the expression of either PDGF chain, IGF-I or II, ECGF, or bFGF were detectable [37].
  • The immunostaining patterns were very similar for aFGF and bFGF for each organ and at each stage [18].
  • Stimulation with bFGF alone had no effect on the activity of either p38 or Akt but markedly enhanced p38 phosphorylation mediated by sst(2(a)) receptors, suggesting that a complex interplay exists between the transduction cascades activated by these distinct receptor types [20].
  • Ligand binding studies indicated that elastase treatment decreased total binding of (125)I-bFGF to the cell surface and affected both fibroblast growth factor receptor and heparan sulfate proteoglycan (HSPG) binding sites [23].
  • Mutation of residues Thr(453) and Thr(739) in Sp1 (amino acids phosphorylated by ERK) blocked FGF-2 repression of PDGFR-alpha transcription [38].
 

Analytical, diagnostic and therapeutic context of Fgf2

  • However, extensive sequence analysis of the promoter and coding regions of the SHR and HHR Fgf2 genes failed to reveal any nucleotide variations between strains [1].
  • Immunoblotting of crude and heparin-bound embryo extracts revealed faint bands at the expected 17-18-kD and predominant bands at an apparent molecular mass of 26 to 28-kD (despite reducing conditions) using multiple specific antibodies for aFGF and bFGF [18].
  • In situ hybridizations showed that the elevation of bFGF and CNTF was localized to the vicinity of the lesion [22].
  • Western blot analysis of I-kappaBalpha and I-kappaBbeta, inhibitors of NF-kappaB, indicated that I-kappaBalpha degradation, rather than I-kappaBbeta degradation, was important in NF-kappaB activation after the stimulation of TRAP and bFGF [32].
  • To begin to understand the role of these growth factors in brain development, the effects of aFGF and bFGF on dissociated cell cultures prepared from embryonic and neonatal rat brain were studied [39].

References

  1. Sequence analysis of the fibroblast growth factor 2 gene from the spontaneously hypertensive and hypertrophic heart rats. Dwyer, J.P., Kostka, V., Harrap, S.B., Di Nicolantonio, R. Clin. Exp. Hypertens. (2004) [Pubmed]
  2. Glypican-1 is frequently overexpressed in human gliomas and enhances FGF-2 signaling in glioma cells. Su, G., Meyer, K., Nandini, C.D., Qiao, D., Salamat, S., Friedl, A. Am. J. Pathol. (2006) [Pubmed]
  3. Coordination of fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-2 (FGF-2) trafficking to nuclei of reactive astrocytes around cerebral lesions in adult rats. Clarke, W.E., Berry, M., Smith, C., Kent, A., Logan, A. Mol. Cell. Neurosci. (2001) [Pubmed]
  4. Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury. Ozaki, S., Radeke, M.J., Anderson, D.H. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  5. Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells. Okada-Ban, M., Moens, G., Thiery, J.P., Jouanneau, J. Oncogene (1999) [Pubmed]
  6. Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures. Gwinn, R.P., Kondratyev, A., Gale, K. Neuroscience (2002) [Pubmed]
  7. Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise. Gómez-Pinilla, F., So, V., Kesslak, J.P. Neuroscience (1998) [Pubmed]
  8. Fibroblast growth factor induces beta-amyloid precursor mRNA in glial but not neuronal cultured cells. Quon, D., Catalano, R., Cordell, B. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  9. Fibroblast growth factor inhibits locomotor activity as well as feeding behavior of rats. Hotta, M., Kuriyama, H., Arai, K., Takano, K., Shibasaki, T. Eur. J. Pharmacol. (2001) [Pubmed]
  10. Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Heaney, A.P., Horwitz, G.A., Wang, Z., Singson, R., Melmed, S. Nat. Med. (1999) [Pubmed]
  11. Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease. Takayama, H., Ray, J., Raymon, H.K., Baird, A., Hogg, J., Fisher, L.J., Gage, F.H. Nat. Med. (1995) [Pubmed]
  12. Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Faktorovich, E.G., Steinberg, R.H., Yasumura, D., Matthes, M.T., LaVail, M.M. Nature (1990) [Pubmed]
  13. Cloning of the rat fibroblast growth factor-2 promoter region and its response to mitogenic stimuli in glioma C6 cells. Pasumarthi, K.B., Jin, Y., Cattini, P.A. J. Neurochem. (1997) [Pubmed]
  14. Suppression of early growth response factor-1 with egr-1 antisense oligodeoxynucleotide aggravates experimental duodenal ulcers. Khomenko, T., Szabo, S., Deng, X., Jadus, M.R., Ishikawa, H., Osapay, K., Sandor, Z., Chen, L. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  15. GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons. Nakajima, K., Hida, H., Shimano, Y., Fujimoto, I., Hashitani, T., Kumazaki, M., Sakurai, T., Nishino, H. Brain Res. (2001) [Pubmed]
  16. IGF-1 and bFGF reduce glutaric acid and 3-hydroxyglutaric acid toxicity in striatal cultures. Bjugstad, K.B., Zawada, W.M., Goodman, S., Free, C.R. J. Inherit. Metab. Dis. (2001) [Pubmed]
  17. Modulation of fibroblast growth factor-2 receptor binding, dimerization, signaling, and angiogenic activity by a synthetic heparin-mimicking polyanionic compound. Miao, H.Q., Ornitz, D.M., Aingorn, E., Ben-Sasson, S.A., Vlodavsky, I. J. Clin. Invest. (1997) [Pubmed]
  18. Acidic fibroblast growth factor in the developing rat embryo. Fu, Y.M., Spirito, P., Yu, Z.X., Biro, S., Sasse, J., Lei, J., Ferrans, V.J., Epstein, S.E., Casscells, W. J. Cell Biol. (1991) [Pubmed]
  19. Differential regulation of acidic and basic fibroblast growth factor gene expression in fibroblast growth factor-treated rat aortic smooth muscle cells. Alberts, G.F., Hsu, D.K., Peifley, K.A., Winkles, J.A. Circ. Res. (1994) [Pubmed]
  20. Receptor isoforms mediate opposing proliferative effects through gbetagamma-activated p38 or Akt pathways. Sellers, L.A., Alderton, F., Carruthers, A.M., Schindler, M., Humphrey, P.P. Mol. Cell. Biol. (2000) [Pubmed]
  21. Acidic and basic fibroblast growth factors in adult rat heart myocytes. Localization, regulation in culture, and effects on DNA synthesis. Speir, E., Tanner, V., Gonzalez, A.M., Farris, J., Baird, A., Casscells, W. Circ. Res. (1992) [Pubmed]
  22. Injury-induced upregulation of bFGF and CNTF mRNAS in the rat retina. Wen, R., Song, Y., Cheng, T., Matthes, M.T., Yasumura, D., LaVail, M.M., Steinberg, R.H. J. Neurosci. (1995) [Pubmed]
  23. Elastase-mediated release of heparan sulfate proteoglycans from pulmonary fibroblast cultures. A mechanism for basic fibroblast growth factor (bFGF) release and attenuation of bfgf binding following elastase-induced injury. Buczek-Thomas, J.A., Nugent, M.A. J. Biol. Chem. (1999) [Pubmed]
  24. Basic fibroblast growth factor evokes a rapid glutamate release through activation of the MAPK pathway in cultured cortical neurons. Numakawa, T., Yokomaku, D., Kiyosue, K., Adachi, N., Matsumoto, T., Numakawa, Y., Taguchi, T., Hatanaka, H., Yamada, M. J. Biol. Chem. (2002) [Pubmed]
  25. Extracellular signal-regulated kinase pathway is involved in basic fibroblast growth factor effect on angiotensin II-induced Ca(2+) transient in vascular smooth muscle cell from Wistar-Kyoto and spontaneously hypertensive rats. Samain, E., Bouillier, H., Miserey, S., Perret, C., Renaud, J.F., Safar, M., Dagher, G. Hypertension (2000) [Pubmed]
  26. Basic fibroblast growth factor modulates insulin-like growth factor-I, its receptor, and its binding proteins in hypothalamic cell cultures. Pons, S., Torres-Aleman, I. Endocrinology (1992) [Pubmed]
  27. Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer cell line. Inhibition by somatostatin. Bensaïd, M., Tahiri-Jouti, N., Cambillau, C., Viguerie, N., Colas, B., Vidal, C., Tauber, J.P., Estève, J.P., Susini, C., Vaysse, N. Int. J. Cancer (1992) [Pubmed]
  28. Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells. Neufeld, G., Gospodarowicz, D., Dodge, L., Fujii, D.K. J. Cell. Physiol. (1987) [Pubmed]
  29. The Golgi sialoglycoprotein MG160, expressed in Pichia pastoris, does not require complex carbohydrates and sialic acid for secretion and basic fibroblast growth factor binding. Chen, Y.J., Gonatas, N.K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  30. Developmental and cell-type-specific expression of cell surface heparan sulfate proteoglycans in the rat heart. Asundi, V.K., Keister, B.F., Stahl, R.C., Carey, D.J. Exp. Cell Res. (1997) [Pubmed]
  31. The Src homology 2 domain protein Shb transmits basic fibroblast growth factor- and nerve growth factor-dependent differentiation signals in PC12 cells. Karlsson, T., Kullander, K., Welsh, M. Cell Growth Differ. (1998) [Pubmed]
  32. Regulation of vascular smooth muscle cell proliferation by nuclear factor-kappaB and its inhibitor, I-kappaB. Hoshi, S., Goto, M., Koyama, N., Nomoto, K., Tanaka, H. J. Biol. Chem. (2000) [Pubmed]
  33. Basic fibroblast growth factor decreases elastin production by neonatal rat lung fibroblasts. Brettell, L.M., McGowan, S.E. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
  34. Changes in gene expression associated with the bone anabolic effects of basic fibroblast growth factor in aged ovariectomized rats. Power, R.A., Iwaniec, U.T., Wronski, T.J. Bone (2002) [Pubmed]
  35. Basic fibroblast growth factor has rapid bone anabolic effects in ovariectomized rats. Power, R.A., Iwaniec, U.T., Magee, K.A., Mitova-Caneva, N.G., Wronski, T.J. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2004) [Pubmed]
  36. Alterations in fibroblast growth factor receptor expression following brain injury. Reilly, J.F., Kumari, V.G. Exp. Neurol. (1996) [Pubmed]
  37. Growth factor expression in aorta of normotensive and hypertensive rats. Sarzani, R., Brecher, P., Chobanian, A.V. J. Clin. Invest. (1989) [Pubmed]
  38. Fibroblast growth factor-2 represses platelet-derived growth factor receptor-alpha (PDGFR-alpha) transcription via ERK1/2-dependent Sp1 phosphorylation and an atypical cis-acting element in the proximal PDGFR-alpha promoter. Bonello, M.R., Khachigian, L.M. J. Biol. Chem. (2004) [Pubmed]
  39. Effects of acidic and basic fibroblast growth factors (aFGF, bFGF) on glial precursor cell proliferation: age dependency and brain region specificity. Engele, J., Bohn, M.C. Dev. Biol. (1992) [Pubmed]
 
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