Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FGF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1993

Reducing the heterogeneity of chemically conjugated targeted toxins: homogeneous basic FGF-saporin.

Basic fibroblast growth factor-saporin (FGF-SAP) is an extremely potent cytotoxic agent for cells bearing the FGF receptor. For its synthesis, the two free cysteines on the surface of basic FGF are available for linking by disulfide bridge to SAP which has been derivatized with a reactive sulfhydryl. Because of the heterogeneous nature of the synthesis, the resulting conjugate is heterogeneous as judged by gel electrophoresis. We have removed by site-directed mutagenesis one of the reactive cysteines of basic FGF and have purified monoderivatized SAP to use as the reactants. The resulting chemical conjugate shows a single band containing only 1 mol of basic FGF and 1 mol of SAP per molecule. This homogeneous conjugate is a potent cytocidal agent to cells bearing the FGF receptor.

3T3 Cells↗
PubMed1997

FGF-8 is expressed during specific phases of rodent oocyte and spermatogonium development.

We have studied the localization of the expression of FGF-8 mRNA in adult and developing rat and mouse gonads by in situ hybridization. The expression of FGF-8 mRNA was high in oocytes of small and large antral follicles of adult mouse ovaries. No signal was observed in fetal ovaries, or in primordial and atretic follicles of adult ovary. In mouse testis, the FGF-8 mRNA signal could be demonstrated in prespermatogonia during a short period covering the fetal days 15 to 17, but not any more on day 19 of fetal life, or in adult testis. The time course of the expression of FGF-8 mRNA in mouse testis was confirmed by RT-PCR reaction. Corresponding in situ results were obtained by studying rat tissues. The observed germ cell-specific expression of FGF-8 mRNA in maturing oocytes and fetal prespermatogonia suggests that FGF-8, which is a secretory protein, has a paracrine function during the specific phases of the maturation of the follicle and fetal seminiferous epithelium.

Animals↗
PubMed1999

FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4.

We have identified a novel fibroblast growth factor, FGF-19, the most distant member of the FGF family described to date. FGF-19 is a high affinity, heparin dependent ligand for FGFR4 and is the first member of the FGF family to show exclusive binding to FGFR4. Human FGF-19 maps to chromosome 11 q13.1, a region associated with an osteoporosis-pseudoglioma syndrome of skeletal and retinal defects. FGF-19 message is expressed in several tissues including fetal cartilage, skin, and retina, as well as adult gall bladder and is overexpressed in a colon adenocarcinoma cell line.

Adenocarcinoma↗
PubMed1994

Dorsal-ventral differences in Xcad-3 expression in response to FGF-mediated induction in Xenopus.

We have identified a dorsal-ventral difference in the specification of mesoderm in vivo by examining the effect of the dominant-negative FGF receptor on a new member of the Xenopus caudal gene family, Xcad-3. Xcad-3 is expressed throughout the marginal zone during the gastrula stages and serves as a useful marker for events occurring within the mesoderm. Disruption of the FGF signaling pathway by the dominant-negative FGF receptor, disrupts the Xcad-3 expression pattern, eliminating expression preferentially from the dorsal regions of the embryo. We also find that the expression of the Xenopus brachyury homolog, Xbra, is more readily eliminated from the dorsal than the ventral region of the embryo by the dominant-negative FGF receptor, indicating that the observed dorsal-ventral differences are not unique to Xcad-3. These results demonstrate the importance of regional effects on FGF-mediated induction in vivo and suggest that FGF-dependent expression of mesodermal genes depends upon the localization of other factors which establish dorsal-ventral differences within the embryo.

Activins↗
PubMed1999

FGF signaling and the anterior neural induction in Xenopus.

We previously showed that FGF was capable of inducing Xenopus gastrula ectoderm cells in culture to express position-specific neural markers along the anteroposterior axis in a dose-dependent manner. However, conflicting results have been obtained concerning involvement of FGF signaling in the anterior neural induction in vivo using the same dominant-negative construct of Xenopus FGF receptor type-1 (delta XFGFR-1 or XFD). We explored this issue by employing a similar construct of receptor type-4a (XFGFR-4a) in addition, since expression of XFGFR-4a was seen to peak between gastrula and neurula stages, when the neural induction and patterning take place, whereas expression of XFGFR-1 had not a distinct peak during that period. Further, these two FGFRs are most distantly related in amino acid sequence in the Xenopus FGFR family. When we injected mRNA of a dominant-negative version of XFGFR-4a (delta XFGFR-4a) into eight animal pole blastomeres at 32-cell stage, anterior defects including loss of normal structure in telencephalon and eye regions became prominent as examined morphologically or by in situ hybridization. Overexpression of delta XFGFR-1 appeared far less effective than that of delta XFGFR-4a. Requirement of FGF signaling in ectoderm for anterior neural development was further confirmed in culture: when ectoderm cells that were overexpressing delta XFGFR-4a were cocultured with intact organizer cells from either early or late gastrula embryos, expression of anterior and posterior neural markers was inhibited, respectively. We also showed that autonomous neuralization of the anterior-type observed in ectoderm cells that were subjected to prolonged dissociation was strongly suppressed by delta XFGFR-4a, but not as much by delta XFGFR-1. It is thus indicated that FGF signaling in ectoderm, mainly through XFGFR-4, is required for the anterior neural induction by organizer. We may reconcile our data to the current "neural default model," which features the central roles of BMP4 signaling in ectoderm and BMP4 antagonists from organizer, simply postulating that the neural default pathway in ectoderm includes constitutive FGF signaling step.

Animals↗
PubMed2000

Overexpression of FGF-2 alters cell fate specification in the developing retina of Xenopus laevis.

The developing vertebrate retina produces appropriate ratios of seven phenotypically and functionally distinct cell types. Retinal progenitors remain multipotent up until the last cell division, favoring the idea that extrinsic cues direct cell fate. We demonstrated previously that fibroblast growth factor (FGF) receptors are necessary for transduction of signals in the developing Xenopus retina that bias cell fate decisions (S. McFarlane et al., 1998, Development 125, 3967-3975). However, the precise identity of the signal remains unknown. To test whether an FGF signal is sufficient to influence cell fate choices in the developing retina, FGF-2 was overexpressed in Xenopus retinal precursors by injecting, at the embryonic 16-cell stage, a cDNA plasmid encoding FGF-2 into cells fated to form the retina. We found that FGF-2 overexpression in retinal precursors altered the relative numbers of transgene-expressing retinal ganglion cells (RGC) and Müller glia; RGCs were increased by 35% and Müller glia decreased by 50%. In contrast, the proportion of retinal precursors that became photoreceptors was unchanged. Within the photoreceptor population, however, we found a twofold increase in rod photoreceptors at the expense of cone photoreceptors. These data are consistent with an endogenous FGF signal influencing cell fate decisions in the developing vertebrate retina.

Animals↗
PubMed2000

Endogenous and ectopic gland induction by FGF-10.

FGF-10, a member of the fibroblast growth factor family, is expressed in mesodermally derived cell populations during embryogenesis. During normal ocular development, FGF-10 is expressed in the perioptic mesenchyme adjacent to the Harderian and lacrimal gland primordia. In this report, we provide evidence that FGF-10 is both necessary and sufficient to initiate glandular morphogenesis. Lens-specific expression of FGF-10 was sufficient to induce ectopic ocular glands within the cornea. In addition, lacrimal and Harderian glands were not seen in FGF-10 null fetuses. Based on these results we propose that FGF-10 is an inductive signal that initiates ocular gland morphogenesis.

Animals↗
PubMed2001

Misexpression of Fgf-4 in the chick limb inhibits myogenesis by down-regulating Frek expression.

Skeletal muscle development involves an initial period of myoblast replication followed by a phase in which some myoblasts continue to proliferate while others undergo terminal differentiation. The latter process involves the permanent cessation of DNA synthesis, activation of muscle-specific gene expression, and fusion of single cells to generate multinucleated muscle fibres. The in vivo signals regulating the progression through all these steps remain unknown. Fibroblast growth factors (Fgfs) and Fgf receptors comprise a large family whose members have been shown to play multiple roles in the development of skeletal muscle in vitro. Exogenously applied Fgfs are able to stimulate proliferation and suppress myogenic differentiation in cell culture. We sought to determine the role played by Fgf-4 during limb myogenesis in vivo. Fgf-4 transcripts are located at both extremities of myotubes whereas the mRNAs of one of the Fgf receptors, Frek, are detected in mononucleated proliferating myoblasts surrounding the multinucleated fibres. Overexpression of mouse Fgf-4 (mFgf-4) using a replication-competent retrovirus, RCAS, leads to a down-regulation of muscle markers followed by an inhibition of terminal differentiation in limb muscles. Using quail/chick transplantations we were able to follow the muscle cells and found a dramatic decrease in their number after exposure to mFgf-4. Interestingly ectopic mFgf-4 down-regulates Frek transcripts in limb muscle areas. We conclude that overexpression of mFgf-4 inhibits myoblast proliferation, probably by down-regulating Frek mRNAs. This suggests a role for Fgf-4, located at the extremities of the myotubes, where it could be responsible for the absence of Frek mRNA in the muscle fibre.

Animals↗
PubMed1998

Permeable FGF-1 nuclear localization signal peptide stimulates DNA synthesis in various cell types but is cell-density sensitive and unable to support cell proliferation.

An earlier report indicated that a 26-amino-acid peptide (SA), comprised of the nuclear localization signal (NLS) of fibroblast growth factor-1 (FGF-1) and a membrane-permeable peptide, was able to stimulate DNA synthesis after it was taken up by NIH3T3 fibroblasts. Here, we report that SA, but not a mutant with the NLS motif destroyed, induced DNA synthesis in BALB/c3T3 murine fibroblasts, human vascular endothelial (HUVE) cells, and primary cultured hepatocytes, although the activity was weaker than that of FGF-1. The kinetics of SA-induced DNA synthesis and G1 cyclin expression were similar to those elicited by FGF-1, indicating that SA induces cell cycle progression. Kinetic analysis also suggested that SA stimulates only a fraction of the DNA replication in BALB/c3T3 cells. At high cell densities, SA-induced G1 cyclin expression and DNA synthesis were more strongly inhibited than those induced by FGF-1. SA did not induce cell division in HUVE and BALB/c3T3 cells and did not interfere with FGF-1-stimulated proliferation of HUVE cells. These results indicate that SA is able to partially induce cell cycle progression through a contact-inhibition sensitive signaling pathway, but it is insufficient to support cell mitosis. We also suggest that signaling by SA does not interfere with that of FGF-1.

3T3 Cells↗
PubMed1994

Spatial and temporal expression patterns of FGF receptor genes type 1 and type 2 in the developing chick retina.

Fibroblast growth factors are known to influence the growth and differentiation of cultured cells derived from the chick retina. The fibroblast growth factors can interact with a family of at least four closely related receptor kinases. To find a correlation between the presence of fibroblast growth factor receptors and eye development, the patterns of expression of transcripts encoding the type 1 (FGF-R1) and type 2 (FGF-R2) receptors in the developing chick retina have been studied. Northern blot analysis of RNA of the whole retina was used to observe that FGF-R1 transcripts are abundant at embryonic day 4 and then decrease until day 11. After this stage, the level of expression of FGF-R1 increases and its peak of expression at embryonic day 18 is concomitant with the detection of the opsin transcript. FGF-R2 transcript is also detected by Northern blots of RNA of the whole retina until embryonic day 6. However, the re-expression after embryonic day 11 of FGF-R2 could only be demonstrated by PCR studies. The same pattern of expression is observed with in situ hybridization of sagittal sections. The two genes are coexpressed in the pigmented epithelium and in the neural retina during embryonic development. The expression follows the retinal layering according to a gradient from the vitreous humor to the choroid. Quantification of the in situ hybridization signals demonstrates that the pattern of expression of both receptors diverges after embryonic day 6 between the pigmented epithelium and the neuronal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

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.

Traumatic injury to the adult central nervous system initiates a cascade of cellular and trophic events, culminating in the formation of a reactive gliotic scar through which transected axons fail to regenerate. Levels of fibroblast growth factor-2 (FGF-2), a potent gliogenic and neurotrophic factor, together with its full-length receptor, FGF receptor 1 (FGFR1) are coordinately and significantly increased postinjury in both nuclear and cytoplasmic fractions of extracted cerebral cortex biopsies after a penetrant injury. FGFR1 is colocalized with FGF-2 in the nuclei of reactive astrocytes, and here FGF-2 is associated with nuclear euchromatin. 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. However, the precise contribution of nuclear FGF-2/FGFR1 to the pathophysiological response of astrocytes after injury is undetermined.

Active Transport, Cell Nucleus↗
PubMed1997

Identification of a MMTV insertion mutation within the coding region of the Fgf-3 protooncogene.

The Fgf-3 protooncogene (previously called int-2) is a target of proviral insertion mutations in mammary tumors induced by the mouse mammary tumor virus (MMTV). These insertion mutations result in the transcriptional activation of Fgf-3, which is not normally expressed in the adult mammary gland. Previous mapping studies of numerous Fgf-3 insertion mutations have failed to reveal any provirus integrations within the gene coding region. This finding is consistent with the hypothesis that oncogenesis occurs in this system as a consequence of up-regulation of Fgf-3 transcription, rather than from alterations of the gene product. During an analysis of a new cohort of tumors from the WXG-2 mouse strain, a breast tumor was identified which had a MMTV provirus integrated 24 bp upstream of the Fgf-3 stop codon. This insertion mutation generated a fusion transcript which was readily detectable in tumor RNA by RT-PCR. The predicted protein product of this fusion transcript is missing 8 aa of native sequence and contains an additional 8 aa of cryptic MMTV-encoded sequence. These data document the first exception to the generalization that the Fgf-3 coding region is not disrupted by MMTV insertion mutation.

Amino Acid Sequence↗
PubMed2002

Upregulation of FGF-2 in reactive spinal cord astrocytes following unilateral lumbar spinal nerve ligation.

Spinal nerve ligation results in dramatic changes in spinal cord primary C-afferent fibers, which include atrophy with an accompanied decrease in calcitonin-gene-related peptide (CGRP). These changes parallel the activation of astrocytes, which have been implicated in the ensuing neuropathic pain states. As part of an effort to elucidate the role of the downstream effectors of astrocyte reactivity in the context of allodynia, the expression of fibroblast growth factor-2 (FGF-2) was examined following tight ligation of L5 and L6 spinal nerves. FGF-2 is a pleiotropic cytokine that is synthesized and secreted by neurons and astrocytes. FGF-2 immunoreactivity was increased in ipsilateral dorsal horn reactive astrocytes at 1 and 3 weeks following nerve ligation. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) of laser-captured dorsal spinal cord sections revealed an increase in FGF-2 mRNA in the dorsal horn ipsilateral to nerve injury compared to contralateral and SHAM. Furthermore, an increase in FGF-2 mRNA in ispilateral dorsal root ganglia (DRG) was seen by in situ hybridization. These results demonstrate that, in response to ligation-induced injury of sensory neurons, FGF-2 is upregulated in both DRG neurons and in spinal cord astrocytes, suggesting neurotrophic functions of this growth factor following peripheral nerve lesion and possibly in astrocyte-related maintenance of pain states.

Animals↗
PubMed2005

Serum VEGF and b-FGF profiles after tension-free or conventional hernioplasty.

BACKGROUND: Angiogenesis is strongly influenced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), whose production is also regulated by interferon (IFN)-gamma and interleukin (IL)-10. The aim of this study was to evaluate the modifications of serum VEGF, b-FGF, IFN-gamma and IL-10 levels in patients with inguinal hernia undergoing hernioplasty with the Lichtenstein technique (LH) using polypropylene mesh or with Bassini open conventional inguinal hernia repair (BH). MATERIALS AND METHODS: Randomly, 16 patients underwent BH, and 16 were treated with the LH technique using polypropylene mesh. Blood samples were collected 24 h prior to surgery and then 6, 24, 48 and 168 h postoperatively. The serum concentrations of VEGF, b-FGF, IFN-gamma and IL-10 were evaluated. RESULTS: In BH patients, a peak of VEGF synthesis at 6 h with a normalization of this parameter 24 h after surgery has been observed. In the same subjects, b-FGF synthesis increased after surgery reaching significant levels 48 h later. On the contrary, in LH patients, a decrease in the serum VEGF and b-FGF concentrations was detected after surgery and their increase afterwards. IL-10 was increased in both groups 6 h after operation and declined to preoperative levels 24 h afterwards. IFN-gamma enhanced in LH patients 6 h after surgery, whereas no modifications were detected in BH subjects. CONCLUSIONS: This preliminary study shows that VEGF and b-FGF modifications, associated with alterations of cytokine secretion, are detectable in human undergoing hernioplasty, and suggests that they could somehow influence in the wound-healing process.

Adult↗
PubMed2005

Kynurenic acid inhibits the release of the neurotrophic fibroblast growth factor (FGF)-1 and enhances proliferation of glia cells, in vitro.

1. Kynurenic (KYNA) and quinolinic (QUIN) acids are neuroactive tryptophan metabolites formed along the kynurenine pathway: the first is considered a non-competitive antagonist and the second an agonist of glutamate receptors of NMDA type. The affinity of these compounds for glutamate receptors is, however, relatively low and does not explain KYNA neuroprotective actions in models of post-ischemic brain damage. 2. We evaluated KYNA effects on the release of fibroblast growth factor (FGF)-1, a potent neurotrophic cytokine. Because KYNA exhibits a neuroprotective profile in vitro and in vivo, we anticipated that it could function as an autocrine/paracrine inducer of FGF-1 release. Studies were performed in several models of FGF-1 secretion (FGF-1 transfected NIH 3T3 cells exposed to heat shock, A375 melanoma cells exposed to serum starvation, growth factor deprived human endothelial cells). To our surprise, KYNA, at low concentration, inhibited FGF-1 release in all cellular models. QUIN, a compound having opposite effects on glutamate receptors, also reduced this release, but its potency was significantly lower than that of KYNA. 3. KYNA and QUIN also displayed a major stimulatory effect on the proliferation rate of mouse microglia and human glioblastoma cells, in vitro. 4. Our data suggest that minor changes of local KYNA concentration may modulate FGF-1 release, cell proliferation, and ultimately tissue damage in different pathological conditions.

Animals↗
PubMed1986

Evidence for FGF-like growth factor in adult bovine retina: analogies with EDGF I.

Eye Derived Growth Factor (EDGF) is the genus name for growth factor activities found in several ocular tissues. Purification from bovine retina by Cibacron blue affinity chromatography has previously given a fraction which can induce target cell proliferation at doses of 30 ng per ml of culture medium. Radioimmunoassay using a labelled synthetic decapeptide [Tyr 10]--FGF (1-10) including the 9 N terminal amino acids of brain Fibroblast Growth Factor (FGF) indicated that EDGF contained a FGF-like material. Further purification of Cibacron blue purified EDGF with heparin sepharose chromatography yielded two active fractions after elution with a sodium chloride gradient. One fraction named EDGF I eluted between 1.3 and 1.5 M NaCl and accounted for over 50% of the input biological activity and comigrated with purified FGF on SDS PAGE at a molecular weight of 16,000 d as a single band. FGF competed with EDGF I for binding to specific receptors on bovine epithelial lens cells. We conclude that retina contains a growth factor activity (EDGF I) similar if not identical to FGF.

Animals↗
PubMed1992

Coexpression of FGF-5 and bFGF by the retinal pigment epithelium in vitro.

Members of the fibroblast growth factor (FGF) gene family have been proposed to play critical roles in the biology of the outer retina. In this study, in vitro cultures of human retinal pigment epithelial (RPE) cells were surveyed for the expression of FGF gene family members. Northern analysis provided evidence for the expression of the previously reported 7.0 and 3.7 kb basic FGF (bFGF) transcripts and for the 4.0 and 2.1 kb FGF-5 transcripts. Western analysis demonstrated the presence of three bFGF proteins ranging in size from 18 to 26 kDa and three FGF-5 proteins of molecular weights 28.5, 34, and 36 kDa. We were particularly interested in cellular mechanisms which might regulate the steady-state mRNA levels of these genes. It was determined that bFGF message levels decreased with increasing culture density, increased upon serum stimulation and when placed in contact with matrix components found in the extracellular matrix of RPE cells in vivo. In a similar fashion, the steady state mRNA levels for FGF-5 decreased with increasing culture density, increased upon serum stimulation, but appeared to be unaffected by matrix contact.

Blotting, Northern↗
PubMed1992

Identification of four FGF receptor genes in Medaka fish (Oryzias latipes).

Four types of cDNA clones encoding tyrosine kinases highly homologous to mammalian fibroblast growth factor receptors (FGF-R) were isolated from Medaka fish (Oryzias latipes) by the reverse transcription-polymerase chain reaction. Comparison of the four deduced amino acid sequences with four known mammalian FGF-Rs indicated that four FGF-R species corresponding to mammalian FGF-Rs exist universally in vertebrates including fishes, although FGF-R4 might have diverged sequences between fishes and mammals. Each of four FGF-R genes is transcribed to various extents as multiple mRNAs possibly by alternative splicing in adult fishes.

Amino Acid Sequence↗