Diminished Heparin Binding of a Basic Fibroblast Growth Factor Mutant Is Associated with Reduced Receptor Binding, Mitogenesis, Plasminogen Activator Induction, and in vitro Angiogenesis

Biochemistry ◽  
1994 ◽  
Vol 33 (36) ◽  
pp. 10999-11007 ◽  
Author(s):  
Lu-Yuan Li ◽  
Michal Safran ◽  
David Aviezer ◽  
Peter Boehlen ◽  
Andrew P. Seddon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
In Vitro Angiogenesis

Vascular endothelial growth factor-induced in vitro angiogenesis and plasminogen activator expression are dependent on endogenous basic fibroblast growth factor

1997 ◽  
Vol 110 (18) ◽  
pp. 2293-2302 ◽  
Author(s):  
S.J. Mandriota ◽  
M.S. Pepper
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Endothelial Growth Factor ◽  
In Vitro Angiogenesis

Induction of in vitro angiogenesis and upregulation of urokinase- and tissue type-plasminogen activator (uPA, tPA) expression are two hallmarks of vascular endothelial growth factor (VEGF) activity on cultured endothelial cells. We report here that neutralizing antibodies to basic fibroblast growth factor (bFGF) inhibit VEGF-induced in vitro angiogenesis in bovine microvascular endothelial (BME) cells. Analysis of VEGF receptor-2 (VEGFR-2) expression revealed no alteration in VEGFR-2 mRNA or total protein in anti-bFGF antibody-treated BME or bovine aortic endothelial (BAE) cells. Ethidium bromide/agarose gel electrophoresis on the cytosolic fraction of BME cells revealed a basal level of fragmented DNA that was increased by anti-bFGF antibodies to an extent not exceeding that observed in parallel cultures incubated with concentrations of transforming growth factor-ss1 that increase VEGF-induced in vitro angiogenesis. In both BME and BAE cells, antibodies to bFGF also decreased basal levels of cell-associated uPA activity, and completely blocked the VEGF-mediated increase in uPA and tPA expression observed in parallel cultures incubated with VEGF alone. In contrast, PA inhibitor-1 expression was strongly upregulated in BME and BAE cells incubated with antibodies to bFGF, either alone or in combination with VEGF. These findings demonstrate that: (1) VEGF-induced in vitro angiogenesis and PA expression are dependent on endogenous bFGF, (2) that this phenomenon is not mediated by a decrease in VEGFR-2 expression and that apoptosis does not necessarily correlate with inhibition of invasion, and (3) that inhibition of endogenous bFGF in VEGF-treated cells results in a net antiproteolytic (and possibly also anti-adherent) effect, which could account in part for the inhibitory effect of the anti-bFGF antibodies. These findings point to a novel and unsuspected role for endogenous bFGF in regulating VEGF-induced in vitro angiogenesis.

scholarly journals In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases.

1989 ◽  
Vol 108 (2) ◽  
pp. 671-682 ◽  
Author(s):  
P Mignatti ◽  
R Tsuboi ◽  
E Robbins ◽  
D B Rifkin
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Cell Invasion ◽  
Tissue Type ◽  
Human Amniotic Membrane ◽  
Fibroblast Growth ◽  
Vitro Assay

The role of basic fibroblast growth factor-(bFGF) induced proteinases in basement membrane (BM) invasion by bovine capillary endothelial (BCE) cells was studied using a quantitative in vitro assay previously described (Mignatti et al., 1986). 125I-iododeoxyuridine-labeled BCE cells were grown for 72 h on the human amnion BM, and cell invasion was determined by measuring the radioactivity associated with the tissue after removal of the noninvasive cell layer. BCE cells were noninvasive under normal conditions. Addition of human bFGF to either the BM or to the stromal aspect of the amnion induced BCE cell invasion with a dose-dependent response. This effect was maximal in the presence of 70 ng/ml bFGF, and was inhibited by anti-FGF antibody. Transforming growth factor beta, as well as plasmin inhibitors and anti-tissue type plasminogen activator antibody inhibited BCE cell invasion. The tissue inhibitor of metalloproteinases, 1-10 phenanthroline, anti-type IV and anti-interstitial collagenase antibodies had the same effect. On the contrary, anti-stromelysin antibody and Eglin, an inhibitor of elastase, were ineffective. The results obtained show that both the plasminogen activator-plasmin system and specific collagenases are involved in the invasive process occurring during angiogenesis.

scholarly journals Identification and concerted function of two receptor binding surfaces on basic fibroblast growth factor required for mitogenesis.

1994 ◽  
Vol 269 (43) ◽  
pp. 26879-26884
Author(s):  
B A Springer ◽  
M W Pantoliano ◽  
F A Barbera ◽  
P L Gunyuzlu ◽  
L D Thompson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Fibroblast Growth

Basic fibroblast growth factor induces retinal pigment epithelium to generate neural retina in vitro

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 577-588 ◽  
Author(s):  
C. Pittack ◽  
M. Jones ◽  
T.A. Reh
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Retinal Pigment ◽  
Neural Retina ◽  
Phenotypic Switching ◽  
Surgical Removal ◽  
Fibroblast Growth ◽  
Neuronal Progenitors

During embryogenesis, the cells of the eye primordium are initially capable of giving rise to either neural retina or pigmented epithelium (PE), but become restricted to one of these potential cell fates. However, following surgical removal of the retina in embryonic chicks and larval amphibians, new neural retina is generated by the transdifferentiation, or phenotypic switching, of PE cells into neuronal progenitors. A recent study has shown that basic fibroblast growth factor (bFGF) stimulates this process in chicks in vivo. To characterize further the mechanisms by which this factor regulates the phenotype of retinal tissues, we added bFGF to enzymatically dissociated chick embryo PE. We found that bFGF stimulated proliferation and caused several morphological changes in the PE, including the loss of pigmentation; however, no transdifferentiation to neuronal phenotypes was observed. By contrast, when small sheets of PE were cultured as aggregates on a shaker device, preventing flattening and spreading on the substratum, we found that a large number of retinal progenitor cells were generated from the PE treated with bFGF. These results indicate that bFGF promotes retinal regeneration in vitro, as well as in ovo, and suggest that the ability of chick PE to undergo transdifferentiation to neuronal progenitors appears to be dependent on the physical configuration of the cells.

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