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

• A shorter latency period for in vivo tumor formation and abundant spontaneous lung metastases were only seen if nuclear FGF-2-producing cells were injected subcutaneously into nude mice [5].
• Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures [6].
• The intensification of the physical activity component of the task by massed or intensive training resulted in greater increases in basic fibroblast growth factor messenger RNA for both learning and yoked groups, but levels of basic fibroblast growth factor messenger RNA in the learning group remained higher than yoked only in the cerebellum [7].
• These results suggest that basic fibroblast growth factor may contribute to amyloidosis of Alzheimer's disease [8].
• These changes, as well as inhibition of body weight gain, were also found during a 6-day period of chronic i.c.v. infusion of bFGF at a dose of 20 ng/h. These results indicate that bFGF as both bolus i.c.v. injection and chronic i.c.v. infusion inhibits not only feeding behavior but also locomotor activity in rats [9].

High impact information on Fgf2

• As bFGF and estrogen both induce pttg, and pttg expression coincides with the early lactotrophic hyperplastic response, angiogenesis and prolactinoma development, we propose a previously unknown paracrine growth factor-mediated mechanism for pituitary tumor pathogenesis and potentially other estrogen-regulated tumors [10].
• We also demonstrate that pttg expression is induced by bFGF, and show concordant pttg and bFGF expression in experimental and human pituitary adenomas [10].
• Results show that bFGF-producing cells grafted together with fetal dopamine neurons have potent growth-promoting effects on the implanted neurons in vivo [11].
• Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease [11].
• Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor [12].

Chemical compound and disease context of Fgf2

• Cloning of the rat fibroblast growth factor-2 promoter region and its response to mitogenic stimuli in glioma C6 cells [13].
• We wanted to determine the effect of egr-1 antisense oligonucleotide on cysteamine-induced duodenal ulcers as well as on the expression of bFGF, PDGF, and VEGF, of which synthesis is modulated by Egr-1 [14].
• Data suggest that bFGF is a minor, while GDNF is a major component of trophic activity for DAergic neurons in DA-depleted striatum, and increased bFGF and GDNF levels may be mediated partly by reactive gliosis [15].
• Striatal neurons were rescued from death by bFGF and IGF-1 but not by glutamate antagonist, suggesting that toxicity in this embryonic system is not necessarily mediated by glutamate receptors [16].
• IGF-1 and bFGF reduce glutaric acid and 3-hydroxyglutaric acid toxicity in striatal cultures [16].

Biological context of Fgf2

• Previous reports of elevated FGF2 mRNA levels in the SHR, led us to hypothesise that nucleotide sequence variations occurring in the coding regions or in putative transcriptional factor binding sites within the Fgf2 promoter might play a role in cardiac hypertrophy in this strain [1].
• Modulation of fibroblast growth factor-2 receptor binding, dimerization, signaling, and angiogenic activity by a synthetic heparin-mimicking polyanionic compound [17].
• In the present investigation, we used immunoblotting and immunochemistry to assess the cellular and tissue distributions of aFGF and bFGF in 11-20-d rat embryos [18].
• Differential regulation of acidic and basic fibroblast growth factor gene expression in fibroblast growth factor-treated rat aortic smooth muscle cells [19].
• The sst(2(a)) receptor-mediated ATF-2 activation and inhibition of proliferation induced by basic fibroblast growth factor (bFGF) were dependent on prolonged phosphorylation of p38 [20].

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

• Pretreatment with 8 M urea yielded 18-20-kD aFGF and bFGF and some 24-26-kD bFGF [18].
• Basic fibroblast growth factor evokes a rapid glutamate release through activation of the MAPK pathway in cultured cortical neurons [24].
• 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 [23].
• 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 [25].
• On the other hand, b-FGF stimulated the Ang II-induced Ca(2+) influx in both strains [25].

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

• Tyrosine phosphorylation of the p13 Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target protein in response to bFGF was strongly inhibited by Shb overexpression, without correlating with the corresponding rate of neurite outgrowth [31].

Co-localisations of Fgf2

• FGFR1 is colocalized with FGF-2 in the nuclei of reactive astrocytes, and here FGF-2 is associated with nuclear euchromatin [3].

Regulatory relationships of Fgf2

• The phosphorylation of ERK1/2 was rapidly induced by TRAP and bFGF but not by TNF-alpha [32].
• Our studies indicate that exogenous and endogenous bFGF can suppress elastin production by LF [33].
• These in vivo results suggest that bFGF treatment upregulates gene expression for IGF-I, which may mediate, at least in part, the increased gene expression for bone matrix proteins and the bone anabolic effects of bFGF in aged ovx rats [34].
• Gene expression for TGF-beta1 was unchanged at early times and only significantly upregulated by a relatively modest 30% in OVX rats treated with bFGF for 10 days [35].
• Basic FGF was detected in the nuclei of cells staining for FGFR, suggesting that FGFR-expressing astrocytes also contained bFGF [36].

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