scholarly journals Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor-2 signaling impairment in the aged neurogenic niche

2017 ◽  
Vol 142 (4) ◽  
pp. 534-544 ◽  
Author(s):  
Taihei Yamada ◽  
Aurelien Kerever ◽  
Yusuke Yoshimura ◽  
Yuji Suzuki ◽  
Risa Nonaka ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Neurogenic Niche

scholarly journals Highly Sulfated Nonreducing End-derived Heparan Sulfate Domains Bind Fibroblast Growth Factor-2 with High Affinity and Are Enriched in Biologically Active Fractions

2011 ◽  
Vol 286 (22) ◽  
pp. 19311-19319 ◽  
Author(s):  
Hicham Naimy ◽  
Jo Ann Buczek-Thomas ◽  
Matthew A. Nugent ◽  
Nancy Leymarie ◽  
Joseph Zaia
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Ternary Complex ◽  
Biologically Active ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
High Affinity ◽  
Symmetrical Model ◽  
Asymmetrical Model

Human fibroblast growth factor-2 (FGF2) regulates cellular processes including proliferation, adhesion, motility, and angiogenesis. FGF2 exerts its biological function by binding and dimerizing its receptor (FGFR), which activates signal transduction cascades. Effective binding of FGF2 to its receptor requires the presence of heparan sulfate (HS), a linear polysaccharide with N-sulfated domains (NS) localized at the cell surface and extracellular matrix. HS acts as a platform facilitating the formation of a functional FGF-FGFR-HS ternary complex. Crystal structures of the signaling ternary complex revealed two conflicting architectures. In the asymmetrical model, two FGFs and two FGFRs bind a single HS chain. In contrast, the symmetrical model postulates that one FGF and one FGFR bind to the free end of the HS chain and dimerization require these ends to join, bringing the two half-complexes together. In this study, we screened a hexasaccharide HS library for compositions that are able to bind FGF2. The library was composed primarily of NS domains internal to the HS chain with minor presence of non-reducing end (NRE) NS. The binders were categorized into low versus high affinity binders. The low affinity fraction contained primarily hexasaccharides with low degree of sulfation that were internal to the HS chains. In contrast, the high affinity bound fraction was enriched in NRE oligosaccharides that were considerably more sulfated and had the ability to promote FGFR-mediated cell proliferation. The results suggest a role of the NRE of HS in FGF2 signaling and favor the formation of the symmetrical architecture on short NS domains.

scholarly journals Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2

2021 ◽  
Author(s):  
Carola Sparn ◽  
Eleni Dimou ◽  
Annalena Meyer ◽  
Roberto Saleppico ◽  
Sabine Wegehingel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Structural Basis ◽  
Limiting Factor ◽  
Fibroblast Growth ◽  
Unconventional Secretion ◽  
Rate Limiting

Fibroblast Growth Factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. Unexpectedly, we found that among the diverse sub-classes consisting of syndecans, perlecans, glypicans and others, Glypican-1 (GPC1) is both the principle and rate-limiting factor that drives unconventional secretion of FGF2. By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression.

Heparan sulfate proteoglycan promotes fibroblast growth factor-2 function for ischemic heart repair

2019 ◽  
Vol 7 (12) ◽  
pp. 5438-5450 ◽  
Author(s):  
Jiajia Shi ◽  
Caixia Fan ◽  
Yan Zhuang ◽  
Jie Sun ◽  
Xianglin Hou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Heparan Sulfate Proteoglycan ◽  
Ischemic Heart ◽  
Fibroblast Growth Factor 2 ◽  
Sulfate Proteoglycan ◽  
Fibroblast Growth ◽  
Heart Repair

HSPG is a bio-scaffold promoting the myocardial binding and bioactivity of bFGF for MI repair.

scholarly journals Heparin and heparan sulfate increase the radius of diffusion and action of basic fibroblast growth factor.

1990 ◽  
Vol 111 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
R Flaumenhaft ◽  
D Moscatelli ◽  
D B Rifkin
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Morphological Changes ◽  
Fibroblast Growth ◽  
Soluble Phase ◽  
Heparan Sulfates ◽  
Sulfate Complexes

The radius of diffusion of basic FGF (bFGF) in the presence and in the absence of the glycosaminoglycans heparin and heparan sulfate was measured. Iodinated 125I-bFGF diffuses further in agarose, fibrin, and on a monolayer of bovine aortic endothelial (BAE) cells in the presence of heparin than in its absence. Heparan sulfates affected the diffusion of 125I-bFGF in a manner similar to, though less pronounced than, heparin. When applied at the center of a monolayer of BAE cells, bFGF plus heparin stimulated morphological changes at a 10-fold greater radius than bFGF alone. These results suggest that bFGF-heparin and/or heparan sulfate complexes may be more effective than bFGF alone in stimulating cells located away from the bFGF source because the bFGF-glycosaminoglycan complex partitions into the soluble phase rather than binding to insoluble glycosaminoglycans in the extracellular matrix. Thus, the complex of bFGF and glycosaminoglycan may represent one of the active forms of bFGF in vivo.

scholarly journals Cell Density-Dependent Fibroblast Growth Factor-2 Signaling Regulates Syndecan-4 Expression in Cultured Vascular Endothelial Cells

2020 ◽  
Vol 21 (10) ◽  
pp. 3698 ◽  
Author(s):  
Takato Hara ◽  
Shiori Yabushita ◽  
Chika Yamamoto ◽  
Toshiyuki Kaji
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Cell Density ◽  
Vascular Endothelial Cells ◽  
Fibroblast Growth Factor 2 ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Density Dependent

Syndecan-4 is a member of the syndecan family of transmembrane heparan sulfate proteoglycans, and is involved in cell protection, proliferation, and the blood coagulation-fibrinolytic system in vascular endothelial cells. Heparan sulfate chains enable fibroblast growth factor-2 (FGF-2) to form a complex with its receptor and to transduce the cell growth signal. In the present study, bovine aortic endothelial cells were cultured, and the intracellular signal pathways that mediate the regulation of syndecan-4 expression in dense and sparse cultures by FGF-2 were analyzed. We demonstrated the cell density-dependent differential regulation of syndecan-4 expression. Specifically, we found that FGF-2 upregulated the synthesis of syndecan-4 in vascular endothelial cells via the MEK1/2-ERK1/2 pathway in dense cell cultures, with only a transcriptional induction of syndecan-4 at a low cell density via the Akt pathway. This study highlights a critical mechanism underlying the regulation of endothelial cell functions by proteoglycans.

scholarly journals Laminin α5 Chain Metastasis- and Angiogenesis-Inhibiting Peptide Blocks Fibroblast Growth Factor 2 Activity by Binding to the Heparan Sulfate Chains of CD44

2005 ◽  
Vol 65 (22) ◽  
pp. 10494-10501 ◽  
Author(s):  
Suguru Hibino ◽  
Masahiko Shibuya ◽  
Matthew P. Hoffman ◽  
Jean A. Engbring ◽  
Rydhwana Hossain ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

Interactions That Influence the Binding of Synthetic Heparan Sulfate Based Disaccharides to Fibroblast Growth Factor-2

2014 ◽  
Vol 9 (8) ◽  
pp. 1712-1717 ◽  
Author(s):  
Yi-Ching Li ◽  
I-Hsin Ho ◽  
Chiao-Chu Ku ◽  
Yong-Qing Zhong ◽  
Yu-Peng Hu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

scholarly journals Common Binding Sites for β-Amyloid Fibrils and Fibroblast Growth Factor-2 in Heparan Sulfate from Human Cerebral Cortex

1999 ◽  
Vol 274 (43) ◽  
pp. 30631-30635 ◽  
Author(s):  
Birgitta Lindahl ◽  
Camilla Westling ◽  
Guillermo Giménez-Gallego ◽  
Ulf Lindahl ◽  
Markku Salmivirta
Keyword(s):  
Cerebral Cortex ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Binding Sites ◽  
Amyloid Fibrils ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Human Cerebral Cortex ◽  
Β Amyloid
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