Disease relevance of Fgf1

• AXC/SSh rat prostate cancer cells elaborate heat-sensitive, heparin-binding mitogens which include members of the fibroblast growth factor (FGF)-like family of growth factors [1].
• Pertussis toxin-sensitive G-proteins inhibit fibroblast growth factor-induced signaling in pancreatic acini [2].
• Histological evaluations after treatment with the non-mitogenic fibroblast growth factor 1 showed that it did not generate the severe hyperplasia and connective tissue disorganization observed with the native mitogenic proteins [3].
• The idea is discussed that sympathetic activation induced either by endogenous aFGF after feeding or by exogenously administered aFGF may play roles both in energy expenditure after overeating and in the modulation of immune functions [4].
• The goal of this study was to examine the ability of basic fibroblast growth factor (FGF-2) to promote reactivity and/or proliferation of astrocytes in vivo following brain injury, and the possible mechanisms involved [5].

Psychiatry related information on Fgf1

• Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise [6].
• Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex [7].
• Fibroblast growth factor inhibits locomotor activity as well as feeding behavior of rats [8].
• The fibroblast growth factor system and mood disorders [9].
• Enhancement of slow wave sleep parallel to the satiating effect of acidic fibroblast growth factor in rats [10].

High impact information on Fgf1

• Structure of a heparin-linked biologically active dimer of fibroblast growth factor [11].
• These findings show that a point mutation in the FGF receptor selectively eliminates activation of PLC gamma and that neither Ca2+ mobilization nor PtdIns hydrolysis are required for FGF-induced mitogenesis [12].
• Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules [13].
• Here we demonstrate that basic fibroblast growth factor (FGF) administered into the brain reduces the death of cholinergic neurons in the medial septum and diagonal band of Broca after transection of their axons, in both young adult and aged rats [14].
• These results indicate a possible function for FGF in the normal support of basal forebrain cholinergic neurons, but its range of activity could be wider, for FGF also supports noncholinergic neurons in vitro, it is localized in many of the central nervous system neurons, and it is found in relatively high concentrations in the brain [14].

Chemical compound and disease context of Fgf1

• The relative and absolute bFGF or aFGF concentrations necessary for half-maximum stimulation of prostate cancer or normal rat kidney fibroblast cell thymidine incorporation were comparable to that known to effect half-maximum increase in proliferation of mesoderm-derived cells [1].
• Neither fibroblast growth factor-1 nor fibroblast growth factor-2 is an androgen receptor coactivator in androgen-resistant prostate cancer [15].
• Using cultured rat cerebellar granule cells, we investigated whether BDNF and FGF2 prevent NMDA toxicity by downregulating NMDA receptor function [16].
• We have studied by immunohistochemistry HBGF-1 and -2 expression in normal rat liver and in carbon tetrachloride (CCl4)-induced fibrosis [17].
• Fibroblast growth factor-induced increases in calcium currents in the PC12 pheochromocytoma cell line are tyrosine phosphorylation dependent [18].

Biological context of Fgf1

• 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 [19].
• Overexpression of these proteins in transfected cell lines can result in autocrine transformation; therefore, the precise control of fibroblast growth factor gene expression in the vessel wall may be an important mechanism regulating vascular cell growth [20].
• Expression of fibroblast growth factors and fibroblast growth factor receptors by adult cardiac myocytes that survive the shock and "dedifferentiation" of culturing may contribute to DNA synthesis and, by analogy, to other cell types, to regulation of ribosomal and actin genes, and to cell survival [21].
• However, the HS from the culture medium of the mammary fibroblasts and the myoepithelial-like cells possessed both a fast/high and a slow/low binding site and could not activate bFGF, although it could potentiate the growth-stimulatory activity of aFGF [22].
• The nucleotide sequence of rat heparin binding growth factor 1 (HBGF-1) [23].

Anatomical context of Fgf1

• Statistical analysis of the increase in process growth revealed that aFGF with heparin contributed to both neurite initiation and elongation [24].
• These results suggest that aFGF has a potent influence on the outgrowth of processes by a neuron in the mammalian central nervous system [24].
• The mean number of glial cells, identified with polyclonal antiserum against glial fibrillary acidic protein, was slightly increased in cultures receiving aFGF plus heparin, but this effect was variable, and these glial cells were not in contact with the solitary RGCs that were scored for regeneration of processes [24].
• Acidic fibroblast growth factor enhances regeneration of processes by postnatal mammalian retinal ganglion cells in culture [24].
• Differential regulation of acidic and basic fibroblast growth factor gene expression in fibroblast growth factor-treated rat aortic smooth muscle cells [20].

Associations of Fgf1 with chemical compounds

• 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 [19].
• Pretreatment with 8 M urea yielded 18-20-kD aFGF and bFGF and some 24-26-kD bFGF [19].
• 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].
• In contrast, C3, D1, T1, or T5 cell-secreted mitogens enhanced proliferation of T1 and T5 cells, and proliferation of D1, T1, and T5 cells was enhanced by bFGF, aFGF, and EGF [1].
• FGF-1 induced the expression of HO-1 in cultured rat spinal cord astrocytes, which was dependent on FGF receptor activation and prevented by cycloheximide [25].

Physical interactions of Fgf1

• The potent gliogenic and neurotrophic fibroblast growth factor (FGF)-2 signals through a receptor complex comprising high-affinity FGF receptor (FGFR)1 with heparan sulphate proteoglycans (HSPGs) as co-receptors [26].
• We conclude that IL-1 beta interacts with FGF-2 to amplify the proliferation of primary rat aortic smooth muscle cells, an effect that may be important in vascular smooth muscle cell proliferation following vascular injury [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].
• Trk receptor binding and neurotrophin/fibroblast growth factor (FGF)-dependent activation of the FGF receptor substrate (FRS)-3 [29].
• Strong activation of PLC via 5-HT2 receptors does however contribute to the synergy observed between 5-HT (Gi-coupled pathway) and fibroblast growth factor (tyrosine kinase-activated pathway) on DNA synthesis reinitiation in transfected cells [30].

Enzymatic interactions of Fgf1

• This 79-kDa FGF receptor was not tyrosine-phosphorylated in response to FGF-1 stimulation, while the 128-kDa FGF receptor was recognized by anti-phosphotyrosine antibody under the same conditions [31].
• Nerve growth factor and fibroblast growth factor selectively activate a protein kinase that phosphorylates high molecular weight microtubule-associated proteins. Detection, partial purification, and characterization in PC12 cells [32].

Regulatory relationships of Fgf1

• Basic fibroblast growth factor and N-cadherin maintain rat granulosa cell and ovarian surface epithelial cell viability by stimulating the tyrosine phosphorylation of the fibroblast growth factor receptors [33].
• Our results suggest that a restricted population of neuroblasts respond to FGF2 in a temporally regulated fashion by proliferating and increasing Otx2 expression [34].
• Furthermore U0126 treatment entirely blocked nerve growth factor-induced ERK1/2 activation in MGC, as well as FGF2-induced ERK1/2 activation in cerebral glial cells [35].
• Growth hormone-releasing factor and fibroblast growth factor regulate somatostatin gene expression [36].
• These data and our results demonstrate that mesangial cells produce and release FGF2( )after injury and that during the proliferative phase these cells upregulate FGFR in vivo [37].

Other interactions of Fgf1

• The immunostaining patterns were very similar for aFGF and bFGF for each organ and at each stage [19].
• Unlike FGF-2, the distribution of FGFR1 mRNA correlates well with the presence of the immunoreactive receptor [38].
• Astroglial cells from all brain regions showed a slight FGF-mediated increase in 5-bromo-2'-desoxy-uridine (BrdU) incorporation, which was abolished upon co-treatment with TGF-beta3 [39].
• Transforming growth factor-beta 1 (TGF-beta 1), which inhibits some effects of FGFs, increased NGF synthesis in concert with aFGF [40].
• Here, we examined whether fibronectin (FN) and FGF can cooperate for neuronal adhesion and neurite outgrowth [41].

Analytical, diagnostic and therapeutic context of Fgf1

• 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].
• Because FGF-1 potently activates astroglia and exerts a direct neuroprotection after spinal cord injury or axotomy, we examined whether it regulated the expression of inducible and cytoprotective heme oxygenase-1 (HO-1) enzyme in astrocytes [25].
• 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 [42].
• Addition of aFGF and heparin or bFGF alone to serum-free cultures of the dissociated Embryonic Day (E) 14.5 mesencephalon stimulates cell proliferation, as judged by [3H]thymidine autoradiography, leading to a maximal 75-fold increase in the total number of cells [42].
• In situ hybridization and immunohistochemistry were used to map gene expression and protein distribution of basic fibroblast growth factor (FGF-2) in the hypothalamic-pituitary system [38].

References