Turnover of Functional Basic Fibroblast Growth Factor Receptors on the Surface of BHK and NIH 3T3 Cells

Moscatelli, David; Devesly, Pierre

doi:10.3109/08977199009037499

Cited by 21 publications

(10 citation statements)

References 40 publications

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“…This is consistent with previous data demonstrating that FGFRs were constantly turning over in the presence or in the absence of ligand (38). In contrast, we showed that FGFR1 was more rapidly and to a greater extent activated by secreted FGF1 in aged RPE cells than in early passage RPE cells.…”

Section: Erk2 Activation and Synthesis In Aged Rpe Cellssupporting

confidence: 93%

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Guillonneau

Bryckaert²,

Launay-Longo³

et al. 1998

Journal of Biological Chemistry

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Retinal-pigmented epithelial (RPE) cell survival is critical to the maintenance of the function of the neural retinal and in the development of various retina degenerations. We investigated molecular mechanisms involved in this function by assessing apoptosis in RPE cells following serum deprivation. Apoptosis induced by serum withdrawal is lower in aged RPE cells because of higher endogenous acidic fibroblast growth factor (FGF1) synthesis and secretion. These experiments examined several aspects of FGF signaling and the contribution of endogenous FGF1 to activation of the extracellular signal-regulated kinase 2 (ERK2). In aged RPE cells, FGFR1 was rapidly activated, and its autophosphorylation followed the kinetics of endogenous FGF1 secretion, before the onset of apoptosis. ERK2 phosphorylation, activity, and de novo synthesis increased at the same time. In marked contrast, no de novo JNK1 synthesis was observed. MEK1 inhibition resulted in lower levels of ERK2 activation and synthesis and higher levels of apoptosis. Treatment with neutralizing anti-FGF1 or blocking anti-FGFR1 antibodies mimics these effects. Thus, this study strongly suggests that the survival-increasing effect of FGF1 in aged RPE cells is because of an autocrine/paracrine loop in which the ERK2 cascade plays a pivotal role. Fibroblast growth factors (FGFs)1 are a family of at least 15 polypeptides that stimulate growth and differentiation in cells of various mesenchymal and ectodermal origins. (for reviews, see Refs. 1-5). Acidic FGF (FGF1) and basic FGF (FGF2) are the prototype members of this family. FGF1 and 2 lack a classic signal peptide (6, 7), implying that they are not secreted by the classical secretion pathway. There is evidence that FGF1 and 2 are exported from the cell and subsequently act as autocrine or paracrine factors (8, 9). FGF1 and 2 exert their effects via high affinity tyrosine kinase receptors (FGFR1-FGFR4) (for reviews, see Refs. 10 -12) and via lower affinity heparan sulfate proteoglycan binding sites (13-15). FGFR activation causes tyrosine phosphorylation of the receptor itself, intracellular proteins including phospholipase C␥ (PLC␥) (16), extracellular signal-regulated kinases (ERKs) (17), and of several uncharacterized proteins of [80][81][82][83][84][85][86][87][88][89][90]19). All cell layers in normal adult retina produce FGF1, as cells no longer differentiate or proliferate. The pattern of FGF1 production suggests that FGF1 may be involved in the regulation of specific spatiotemporal events, including proliferation, migration, differentiation and survival in the retina. In vivo, despite the presence of FGFs in the retinal interphotoreceptor matrix, RPE cells have a limited proliferation capacity consistent with the normal increase in retinal space associated with growth and age. In adult, RPE cells cannot divide in vivo, but they may still require survival factors to inhibit their apoptosis. Cell survival and proliferation may be determined by the amount of factor available and the amount of receptor produc...

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Section: Erk2 Activation and Synthesis In Aged Rpe Cellssupporting

confidence: 93%

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Guillonneau

Bryckaert²,

Launay-Longo³

et al. 1998

Journal of Biological Chemistry

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“…Rather, a most striking phenomenon was the transient disappearance of FGFR2 in FGF2-stimulated cells, unveiling an inhibitory feedback controlling FGF2-dependent signaling in astrocytes. A comparable phenomenon has been reported in NIH 3T3 cell lines [53] , wherein FGFR internalization followed by degradation leads to receptor desensitization. It appears overall that a cell membrane rather than a nuclear FGFR2 accounts for the immunomodulatory actions of LMW-FGF2 in cerebellar astrocytes.…”

Section: Discussionmentioning

confidence: 59%

JNK/ERK/FAK Mediate Promigratory Actions of Basic Fibroblast Growth Factor in Astrocytes via CCL2 and COX2

Lichtenstein¹,

Madrigal

Pujol³

et al. 2012

Neurosignals

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While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is mainly produced by astrocytes and characteristically upregulated in reactive astrocytes. The goal of this study was to characterize the inflammatory actions of FGF2 in astrocytes using primary cultures. We report that FGF2 induced the upregulation of monocyte chemoattractant protein (CCL2) and cyclo-oxygenase type 2 (COX2), and the inhibition of lipopolysaccharide-elicited ICAM1 upregulation. The effects of FGF2 were: (i) dependent on gene transcription as revealed by the concomitant regulation of CCL2 or ICAM1 mRNAs; (ii) mediated by the FGF2 receptor type 2; (iii) dependent on ERK, JNK and FAK, and (iv) NF-ĸB-independent. FGF2 also caused accelerated wound closure dependent on CCL2, COX2, ERK, JNK and FAK in a scratch assay. We conclude that the signaling network triggered by FGF2 in astrocytes converged into accelerating directed motion. It follows that astrocyte migration to injury sites may be a key factor in the repair mechanisms orchestrated by FGF2.

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“…The kinetics of bFGF in the pericellular environment may involve repeated binding and release both from the bFGF tyrosine kinase receptor and from heparan sulfate proteoglycan on the cell surface and within the extracellular matrix (35)(36)(37)(38). This mechanism has been postulated as a means of maintaining multiple molecules of bFGF within a small domain of binding sites (38).…”

Section: Discussionmentioning

confidence: 99%

Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition.

Edelman

Nugent

Karnovsky

1993

Proc. Natl. Acad. Sci. U.S.A.

239

126

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The in vivo mitogenicity of basic fibroblast growth factor (bFGF) for arterial smooth muscle cells relies on the removal ofendothelium, raising the question of whether the endothelium serves as a mechanical barrier preventing contact of circulating bFGF with underlying smooth muscle cells or as a biochemical barrier that produces a local inhibitor of bFGF activity. To better define the role of the intact endothelium in modulating the vascular and tissue deposition of bFGF, we compared the fate of intravenous injections of 12SI-labeled bFGF with perivascular controlled growth factor release. Peak serum bFGF levels were detected within 1 min of injection, and the growth factor was cleared thereafter with a serum half-life of almost 3 min. Polymeric controlled release devices delivered bFGF to the extravascular space without transendothelial transport. Deposition within the blood vessel wall was rapidly distributed circumferentially and was substantially greater than that observed following intravenous injection. The amount of bFGF deposited in arteries adjacent to the release devices was 40 times that deposited in similar arteries in animals who received a single intravenous bolus of bFGF. Endothelial denudation had a minimal effect on deposition following perivascular release, and it increased deposition following intravenous delivery 2-fold. The presence of intimal hyperplasia increased deposition of perivascularly released bFGF 2.4-fold but decreased the deposition of intravenously injected bFGF by 67%. In contrast, bFGF was 5-to 30-fold more abundant in solid organs after intravenous injection than it was following perivascular release. Deposition was greatest in the kidney, liver, and spleen and was substantially lower in the heart and lung. Thus, bFGF is rapidly cleared following intravenous injection and is deposited within both solid organs and the walls of blood vessels. Unlike the mitogenic potential of bFGF within blood vessels, vascular deposition is virtually independent of the presence of endothelium. Perivascular delivery is far more efficient than intravenous delivery at depositing bFGF within the arterial wall, and an increased neointima may provide added substrate for potential bFGF deposition but has limited contact with intravascular growth factor as a result of dilutional and flow-mediated effects.Basic fibroblast growth factor (bFGF) is synthesized by and mitogenic for a variety of cell types, including endothelial cells and smooth muscle cells, and is intensely angiogenic (1)(2)(3)(4)(5). Intravenous infusion of bFGF stimulates endothelial regeneration (6) and smooth muscle cell proliferation (7) after endothelial denudation. The effect on smooth muscle cells was noted only in the absence of endothelium, and it was concluded that the endothelium may serve as a barrier preventing contact of the mitogen, bFGF, with the target, vascular smooth muscle cells (7). We confirmed that bFGF was both angiogenic and mitogenic for vascular smooth muscle cells in vivo and demonstrated that these t...

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Turnover of Functional Basic Fibroblast Growth Factor Receptors on the Surface of BHK and NIH 3T3 Cells

Cited by 21 publications

References 40 publications

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

JNK/ERK/FAK Mediate Promigratory Actions of Basic Fibroblast Growth Factor in Astrocytes via CCL2 and COX2

Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition.

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