Disease relevance of FGF2

• Thus, FGF2 glycation may represent a mechanism responsible for the impairment of angiogenesis in diabetes mellitus [1].
• These results suggest that FGF-1, FGF-2, and PDGF-BB play a role in the signal transduction pathway linking hypoxia to altered NPR-C expression in lung [2].
• Specific binding of basic fibroblast growth factor to basement membrane-like structures and to purified heparan sulfate proteoglycan of the EHS tumor [3].
• CONCLUSIONS: Taken together, these results suggest that FGF2 may play a significant role in maintaining the integrity of the BBB during the progress of HIV associated cerebral endothelial cell damage [4].
• We hypothesized that treatment of human umbilical vein endothelial cells (HUVEC) with FGF2 would protect the cells from gp120-mediated toxicity via endothelial cell survival signalling [4].

High impact information on FGF2

• Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth [5].
• As well as being a potent inducer of cell division in capillary endothelial cells in vitro, bFGF can act as an angiogenic agent in vivo [5].
• It is probably triggered by agents, such as basic fibroblast growth factor (bFGF), thought to be released from tissues adjacent to proliferating capillaries [5].
• Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor [6].
• We found that both bovine aortic and human umbilical vein cells respond to the MAC by releasing basic fibroblast growth factor and platelet-derived growth factor [7].

Chemical compound and disease context of FGF2

• Using the baculovirus system, we expressed TSRs of human TSP1 as either the three domains in tandem (P123) or the third domain alone (P3) and demonstrated that both P123 and P3 at nanomolar concentrations inhibit either basic fibroblast-growth-factor or sphingosine-1-phosphate induced endothelial cell migration [8].
• Curcumin and its derivatives demonstrated significant inhibition of bFGF-mediated corneal neovascularization in the mouse [9].
• 2. Tranilast significantly (P<0.01) inhibited VEGF, basic fibroblast growth factor (bFGF), and hypoxia conditioned media-induced BREC proliferation in a dose dependent manner with IC50's of 22, 82 and 10 microM, respectively [10].
• Corneal neovascularization was induced by implantation of hydron pellets containing bFGF in rat corneal micropockets [11].
• The cells secreted a heparin-binding growth factor and a type-beta transforming growth factor, but their growth in PF-C-F12 was not affected by these factors, or by DNA synthesis factor from Rhodamine fibrosarcoma, basic fibroblast growth factor, insulin, human transferrin, bovine serum albumin, and their combinations [12].

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

• Thus those effects of TGF beta and ACTH on proteoglycan synthesis may participate in an increased ability of adrenocortical cells to bind and respond to bFGF [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 [21].
• Here, we show that FGF-2 added to nuclear extract binds to protein kinase CK2 and nucleolin, a CK2 natural substrate [22].
• Carboxyl-terminal heparin-binding fragments of platelet factor 4 retain the blocking effect on the receptor binding of basic fibroblast growth factor [23].
• Glycation caused a significant reduction in the ability of FGF-2 to bind to the tyrosine kinase receptor and activate signal transduction pathways responsible for both mitogenesis and capillary formation in BAEC [24].

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

• In the presence of exogenous FGF2, addition of a specific anti-FGF1 neutralizing antibody induces a rapid apoptosis of RPE cell cultures [15].
• Immunohistochemistry revealed (a) no FGF2 protein in Sertoli cells (b) moderate cytoplasmic staining in Leydig cells and spermatogonia and (c) strong nuclear and faint cytoplasmic staining in myofibroblasts, in epithelial cells of straight tubules and rete testis and in blood vessels [32].
• Quantitative RT-PCR revealed consistent levels of FGF2 mRNA in parenchymal samples of the bovine testis [32].
• In situ hybridization localized FGF2 transcripts only in a constant fraction of Leydig and Sertoli cells as well as in modified Sertoli cells of the terminal segments [32].
• VSM cells contain 3.7 and 7.0 kilobase bFGF gene transcripts, which are translated into material closely related, if not identical, with bFGF when analyzed by its chromatographic behavior on heparin Sepharose, by immunoblot and by radioimmuno- and radioreceptor assays [33].

References