Disease relevance of FGF2

• Four days after the final dose of growth factor, we found that the production of ganglion cells was induced by co-injection of insulin and FGF2, but not by either insulin or FGF2 alone [1].
• Different aspects of gliosis in retinal Muller glia can be induced by CNTF, insulin, and FGF2 in the absence of damage [2].
• By using viral gene transfer, based on herpes simplex type 1 virus (HSV-1), we show that ectopically applied FGF2 drastically increases the number of cells expressing early hair cell markers during embryonic development in avians [3].
• Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy [4].
• In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human melanoma fragments but had no effect on preexisting vessels [5].

High impact information on FGF2

• Basic fibroblast growth factor, epidermal growth factor, retinoic acid, and transforming growth factor type B1 and B2 were not capable of inducing axial structures [6].
• We identify activin-betaB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin [7].
• It is sufficiently potent to effectively suppress basic fibroblast growth factor-induced corneal neovascularization after systemic administration in mice [8].
• Sustained activation of p38 by FGF-2 was identified in vascular endothelial cells in vivo in the chick chorioallantoic membrane (CAM) [9].
• Overexpression of dominant negative mutants of the p38-activating kinases MKK3 and MKK6 also supported FGF-2-induced tubular morphogenesis [9].

Chemical compound and disease context of FGF2

• The combination of insulin and FGF2 stimulated the regeneration of ganglion cells in kainate- and colchicine-treated retinas [10].
• SB202190 treatment enhanced FGF-2-induced neovascularization in the CAM, but the vessels displayed abnormal features indicative of hyperplasia of endothelial cells [9].

Biological context of FGF2

• We observed that during the induction of transdifferentiation, downregulation of Mitf was not sufficient to induce transdifferentiation at E4 and that FGF2 was required to drive Pax6 protein expression and cell proliferation, both of which are necessary for transdifferentiation [11].
• Furthermore, we show that ectopic Mitf expression is able to protect the RPE from FGF2 induced transdifferentiation by inhibiting Pax6 upregulation [11].
• We have identified eight different basic fibroblast growth factor (bFGF or FGF-2) transcripts which can be grouped into three classes expressed during chicken embryogenesis and in specific adult organs [12].
• We suggest that the primary effect of FGF-2 is an increase in cellular density mediated through cell migration, followed by the expression of dermal condensation-specific genes and cessation of cell proliferation [13].
• Whether FGF1 or FGF2 expression was inhibited the results were the same: a marked reduction in neuronal photoreceptor cells differentiation, an increase in programmed cell death, but no effects on cell proliferation [14].

Anatomical context of FGF2

• Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area [15].
• METHODS: The retina of embryonic day 4 (E4) chicks was removed and a heparin coated bead soaked in fibroblast growth factor 2 (FGF2) was placed into the optic cup [11].
• Temporal dynamics of neurite outgrowth promoted by basic fibroblast growth factor in chick ciliary ganglia [16].
• FGF-2 and FGF-4 can mimic many of the effects of mandibular epithelium from the medial region, including supporting the expression of Msx genes, outgrowth of the mandibular processes and elongation of Meckel's cartilage [17].
• In contrast, bFGF can promote global growth of the neuritic network both in whole ganglia and in dissociated cultures for times up to 48 hr, and this effect is related to an increase in the growth rate of single neurites [16].

Associations of FGF2 with chemical compounds

• Its down-regulation by antisense oligonucleotides and blockade of its signaling pathway (binding to FGF-R1, tyrosine phosphorylation, and ERK inhibition) decreased bcl-x(L) and bcl-2 levels and and enhanced apoptosis, suggesting that endogenous FGF2 supported neuronal survival through a pathway similar to that of exogenous FGF2 [18].
• The heparan sulfate proteoglycans, syndecan-1 and glypican-1 (glypican), are low affinity receptors for fibroblast growth factor 2 (FGF2) [19].
• The angiogenic activity of uPA is significantly inhibited by neutralizing anti-FGF2 antibodies or by pretreatment with phenylmethylsulfonyl fluoride [20].
• Molecular dynamics calculations support the assumption that glycol-split residues act as flexible joints that, while favoring 1:1 binding to FGF2, disrupt the linearity of heparin chains necessary for formation of active complexes with FGFRs [21].
• Resveratrol demonstrated potent inhibition (effective dose50=0.7+/-0.1 microM) of FGF2-induced angiogenesis and tumor growth [22].

Regulatory relationships of FGF2

• CONCLUSIONS: FGF2 stimulates Pax6 expression during induction of transdifferentiation of the RPE through FGFR/MEK/Erk signaling cascade [11].
• Basic fibroblast growth factor or taurine both of which have been reported to stimulate opsin expression in rat retinal cultures and other neurotrophic factors tested (nerve growth factor, brain derived neurotrophic factor) had no effect [23].
• At stage 39, basic fibroblast growth factor induced less marked changes in the accumulation of actin and alpha-actinin [24].
• Immunohistochemical studies revealed that basic fibroblast growth factor inhibited the expression of osteocalcin [25].

Other interactions of FGF2

• Basic fibroblast growth factor (bFGF) is a potent and multifunctional neurotrophic factor that can influence neuronal survival and differentiation [16].
• Furthermore, although the capillary network initiated by VEGF and b-FGF lasts no more than 7 days, addition of a sulfated oligosaccharide significantly amplifies angiogenesis and stabilizes the capillary network of new blood vessels [26].
• The spatiotemporal expression of syndecan-3 during feather development suggests that this cell-surface HSPG may be involved in the response of competent embryonic skin dermis to FGF-2 [13].
• FGFR3 was expressed in all the chondrocyte types, yet strongly increased in the LS, USC, USP, and Ti in that order according to the concentration of FGF2 [27].
• We have examined the consequences of selectively and independently inhibiting FGF1 or FGF2 expression using antisense oligonucleotides in embryonic chick retinal cells, differentiating in vitro [14].

Analytical, diagnostic and therapeutic context of FGF2

• In order to clarify putative sources of FGF2 in embryonic tissues, we detected by in situ hybridization high levels of mRNA expression in notochord, mesonephros and hepatic primordia, and low levels in brain neuroectoderm, corroborated by semiquantitative PCR analysis [28].
• The function of the developmental increase of endogenous FGF2 in the developing chick retina was investigated by using an antisense strategy, using both optic vesicle cultures and in ovo-intravitreal microinjections [29].
• In this work, CAM has been investigated by in situ hybridization with the aim to identify the source(s) of endogenous FGF2 during development [30].
• This was confirmed by Northern blotting and Western blot analysis of the conditioned media in different clones of endothelial cells overexpressing FGF2 and in endothelial cells treated with the recombinant growth factor [31].
• We examined the effects and mechanisms of the flavonoid resveratrol on angiogenesis and tumor growth using the chick chorioallantoic membrane (CAM) model of angiogenesis, the CAM tumor growth model, and the effect on p53 in fibroblast growth factor-2 (FGF2) stimulated human endothelial cells using immunoassay [22].

References