118. CHARACTERISATION OF HEPARAN SULPHATE PROTEOGLYCANS IN THE MATURING CUMULUS OOCYTE COMPLEX

2009 ◽  
Vol 21 (9) ◽  
pp. 37
Author(s):  
L. N. Watson ◽  
M. Sasseville ◽  
R. B. Gilchrist ◽  
D. L. Russell
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Cumulus Cells ◽  
Receptor Interaction ◽  
Heparan Sulphate Proteoglycans ◽  
Tgfβ Superfamily

Many growth factors including members of the transforming growth factor beta (TGFβ) superfamily and epidermal growth factor (Egf)-like ligands signal via interactions with heparan sulphate proteoglycans (HSPGs). Cell surface HSPGs can act by sequestering ligands at their site of action, by presenting a ligand to its signalling receptor, or by preventing ligand-receptor interaction. The oocyte secreted factors (OSF) growth differentiation factor 9 and bone morphogenetic protein 15 are members of the TGFβ superfamily that act selectively on cumulus cells. Conversely Egf-like ligands are secreted by mural granulosa cells and transmit LH-induced signals to cumulus cells. We investigated the possibility that HSPGs contribute to the spatially restricted responses these signals exert on cumulus cells. Syndecan-1 and Glypican-1 are cell surface HSPGs that are involved in numerous biological processes, including growth factor regulation, cell proliferation and differentiation. Microarray analysis showed Syndecan-1 and Glypican-1 mRNA expression induced 6-fold (P=10-9) and 3-fold (P=10-7) respectively in Egf+FSH stimulated cumulus oocyte complexes (COCs). Furthermore, Syndecan-1 and Glypican-1 mRNA were induced 27- and 16-fold respectively in COCs after hCG treatment of mice. Syndecan-1 and Glypican-1 protein was localised specifically to the COC through immunohistochemical analysis. In Vitro Maturation (IVM) of oocytes is a valuable alternative to gonadotropin mediated superovulation, but IVM COCs are less competent than those matured in vivo. Several components of the COC have been shown to be altered in IVM, including the chondroitin sulphate proteoglycan Versican. COCs from mice that underwent IVM in the presence of Egf+FSH and cilostamide for 16 hours had >16 fold reduced mRNA for Syndecan-1 when compared with In Vivo matured COCs. The lack of Syndecan-1 in IVM COCs could reduce signalling capacity of growth factors including OSFs. This may contribute to the reduced capacity of IVM oocytes to fertilise and produce a healthy embryo, and ultimately, a healthy offspring.

Comparison of Release Profiles of Various Growth Factors from Biodegradable Carriers

1998 ◽  
Vol 530 ◽  
Author(s):  
Y. Tabata ◽  
M. Yamamoto ◽  
Y. Ikada
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
The Body ◽  
Bone Morphogenetic Protein 2 ◽  
Biodegradable Hydrogel ◽  
Tgf Β1

AbstractA biodegradable hydrogel was prepared by glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 as a carrier to release basic growth factors on the basis of polyion complexation. Basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) were sorbed from their aqueous solution into the dried gelatin hydrogels to prepare respective growth factor-incorporating hydrogels. Under an in vitro non-degradation condition, approximately 20 % of incorporated bFGF and TGF-β1 was released from the hydrogels within initial 40 min, followed by no further release, whereas a large initial release of BMP-2 was observed. After subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled growth factor in the mouse back, the remaining radioactivity was measured to estimate the in vivo release profile of growth factors. Incorporation into gelatin hydrogels enabled bFGF and TGF-β1 to retain in the body for about 15 days and the retention period well correlated with that of the gelatin hydrogel. Taken together, it is likely that the growth factors ionically complexed with acidic gelatin were released in vivo as a result of hydrogel biodegradation. On the contrary, basic BMP-2 did not ionically interact with acidic gelatin, resulting in no sustained released by the present biodegradable carrier system.

dally, a Drosophila glypican, controls cellular responses to the TGF-beta-related morphogen, Dpp

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4113-4120 ◽  
Author(s):  
S.M. Jackson ◽  
H. Nakato ◽  
M. Sugiura ◽  
A. Jannuzi ◽  
R. Oakes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ectopic Expression ◽  
Cellular Responses ◽  
Growth Factor Signaling ◽  
Tgf Beta ◽  
Morphogenetic Protein

Decapentaplegic (Dpp) is a Drosophila member of the Transforming Growth Factor-beta (TGF-beta)/Bone Morphogenetic Protein (BMP) superfamily of growth factors. Dpp serves as a classical morphogen, where concentration gradients of this secreted factor control patterning over many cell dimensions. Regulating the level of Dpp signaling is therefore critical to its function during development. One type of molecule proposed to modulate growth factor signaling at the cell surface are integral membrane proteoglycans. We show here that division abnormally delayed (dally), a Drosophila member of the glypican family of integral membrane proteoglycans is required for normal Dpp signaling during development, affecting cellular responses to this morphogen. Ectopic expression of dally+ can alter the patterning activity of Dpp, suggesting a role for dally+ in modulating Dpp signaling strength. These findings support a role for members of the glypican family in controlling TGF-beta/BMP activity in vivo by affecting signaling at the cell surface.

Growth factor and somatic cell regulation of mouse gonocyte-derived colony formation in vitro

Reproduction ◽  
2000 ◽  
pp. 85-91 ◽  
Author(s):  
S Hasthorpe ◽  
S Barbic ◽  
PJ Farmer ◽  
JM Hutson
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Colony Formation ◽  
Inhibitory Action ◽  
Transforming Growth Factor ◽  
Epidermal Growth ◽  
Growth Factor Beta

At birth, the mouse gonocyte does not resume mitotic activity for several days in vivo but, in an in vitro clonogenic system, cell division commences soon after culture. Somatic testis cell underlays had potent inhibitory activity on gonocyte-derived colony formation (23 +/- 15% compared with 84 +/- 1% in controls; P = 0.0001) when added to cultures of gonocytes in vitro. A Sertoli cell line, TM4B, had an even more pronounced effect on gonocyte clonogenic capacity, with 1 +/- 1% compared with 72 +/- 17% colony formation in controls (P = 0.0003). Testis cells appeared to have a direct inhibitory effect since testis-conditioned medium did not show a significant reduction in the number of colonies. The observed reduction in colony formation with the testis cell underlay was not accounted for by decreased attachment of gonocytes as simultaneous addition of a single cell suspension of testis cells was still effective in significantly reducing colony number when compared with controls (P = 0.01). Therefore, the observed inhibition exerted by testis cells appears to be a consequence of decreased proliferation of gonocytes. Growth factors belonging to the transforming growth factor beta superfamily which are known to be expressed in testis, such as transforming growth factor beta and epidermal growth factor, did not exert any inhibitory action on gonocyte-derived colony formation when added together or alone. However, a shift to a smaller colony size occurred in the presence of transforming growth factor beta and transforming growth factor beta plus epidermal growth factor, indicating a reduction in colony cell proliferation. Evidence for the expression of the Mullerian inhibiting substance receptor on newborn gonocytes using in situ hybridization was inconclusive. This finding was in agreement with the lack of a direct action of Mullerian inhibiting substance on the formation of gonocyte-derived colonies in vitro. Leukaemia inhibitory factor, alone or in combination with forskolin, had neither an inhibitory nor an enhancing effect on gonocyte-derived colony formation. An in vitro clonogenic method to assay for the proliferation of gonocytes in the presence of specific growth factors, cell lines, testis cell underlays and cell suspensions was used to identify a somatic cell-mediated inhibitor which may be responsible for the inhibitory action on gonocyte proliferation in vivo shortly after birth.

Bone graft substitutes for the promotion of spinal arthrodesis

2001 ◽  
Vol 10 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Gregory A. Helm ◽  
Hayan Dayoub ◽  
John A. Jane
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Bone Graft ◽  
Bone Repair ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Local Bone ◽  
Bone Graft Substitutes ◽  
Autologous Bone

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the “gold standard” for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor–β, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans. The delivery of pluripotent mesenchymal stem cells (MSCs) to regions requiring bone formation is also compelling, and it has been shown to be successful in inducing osteogenesis in numerous pre-clinical studies in rats and dogs. Finally, the identification of biological and nonbiological scaffolding materials is a crucial component of future bone graft substitutes, not only as a delivery vehicle for bone growth factors and MSCs but also as an osteoconductive matrix to stimulate bone deposition directly. In this paper, the currently available bone graft substitutes will be reviewed and the authors will discuss the novel therapeutic approaches that are currently being developed for use in the clinical setting.

Regulation of DNA synthesis in chicken adipocyte precursor cells by insulin-like growth factors, platelet-derived growth factor and transforming growth factor-β

1991 ◽  
Vol 131 (2) ◽  
pp. 203-209 ◽  
Author(s):  
S. C. Butterwith ◽  
C. Goddard
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Igf I ◽  
Tgf Β1 ◽  
Adipocyte Precursor ◽  
Insulin Like Growth Factors

ABSTRACT Adipose tissue growth can occur by both hypertrophy and hyperplasia. The capacity for adipocyte hyperplasia in vivo resides in a population of fibroblast-like adipocyte precursor cells but the regulation of the proliferation of these cells by growth factors has not been well characterized. This study was designed to determine the effects of the insulin-like growth factors (IGF-I and IGF-II), platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) added alone or together on the proliferation of primary adipocyte precursor cells in vitro. Adipocyte precursor cell proliferation measured by [3H]thymidine incorporation into DNA was stimulated by all of these growth factors and was particularly marked with PDGF. IGF-I or IGF-II added together with TGF-β1 produced a greater than additive response and the effect of PDGF was synergistic with that of IGF-I at certain concentrations. Stimulation of proliferation of some cell types by TGF-β has been linked to the secondary production of PDGF but the evidence we have suggests that this is unlikely in chicken adipocyte precursors. DNA synthesis in response to TGF-β1 required only a short exposure to the peptide, and conditioned medium from chicken adipocyte precursor cells previously exposed to TGF-β had no effect on DNA synthesis when added to fresh batches of cells. Addition of TGF-β1 together with PDGF produced a synergistic effect whereas an additive effect would be expected if PDGF mediated the effect of TGF-β1. IGF-I mRNA is expressed in the Ob 1771 preadipocyte cell line during differentiation, in stromalvascular cells from adipose tissue, and TGF-β mRNA is expressed in both proliferating and differentiating 3T3-L1 preadipocytes. Together with the data presented here, this would indicate that these peptides have a role in adipocyte development by an autocrine or paracrine mechanism although the source of PDGF in vivo is at present unknown. Journal of Endocrinology (1991) 131, 203–209

scholarly journals Transforming growth factor-β 1 increases internalization of basic fibroblast growth factor by smooth muscle cells: implication of cell-surface heparan sulphate proteoglycan endocytosis

1995 ◽  
Vol 311 (2) ◽  
pp. 393-399 ◽  
Author(s):  
E Berrou ◽  
R Quarck ◽  
M Fontenay-Roupie ◽  
S Lévy-Toledano ◽  
G Tobelem ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Cell Surface ◽  
Smooth Muscle Cells ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Proteoglycan Synthesis ◽  
Fibroblast Growth ◽  
Tgf Beta

Basic fibroblast growth factor (bFGF) was internalized by smooth muscle cells (SMC) from pig aorta. Correlation between heparin inhibition of binding and late internalization (8 h) implicated low-affinity sites in bFGF internalization. Transforming growth factor-beta 1 (TGF-beta 1) induced a 38% increase in bFGF internalized between 4 and 8 h. While bFGF and/or TGF-beta 1 enhanced cell-surface proteoglycan synthesis, 35S-labelled proteoglycans of the extracellular matrix (ECM) were not affected. This might be explained by the different turnover rates displayed by the two populations of proteoglycans. Although bFGF and/or TGF-beta 1 induced a similar stimulation in cell-surface chondroitin sulphate/dermatan sulphate and heparan sulphate (HS) proteoglycan synthesis, only the turnover of HS proteoglycans was increased. Twice as much HS proteoglycan was internalized in the presence of TGF-beta 1 or bFGF. Furthermore, TGF-beta 1 induced a 43 +/- 12% increase in HS proteoglycan internalized in the presence of bFGF with a parallel 38% increase in bFGF internalization. Overall, the results indicated that bFGF bound to two HS proteoglycan populations. bFGF storage (70% of bFGF bound to SMC) was not affected by TGF-beta 1 under our conditions and involved ECM proteoglycans characterized by a low turnover. bFGF internalization up-regulated by TGF-beta 1 involved cell-surface HS proteoglycan characterized by a high turnover.

scholarly journals Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3360 ◽  
Author(s):  
Fuming Zhang ◽  
Lanhong Zheng ◽  
Shuihong Cheng ◽  
Yanfei Peng ◽  
Li Fu ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Transforming Growth Factor ◽  
Keratan Sulfate ◽  
Heparin Binding ◽  
Chip Surface ◽  
High Affinity ◽  
Sulfo Groups

Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors are heparin-binding proteins (HBPs) that have a high affinity for cell surface heparan sulfate proteoglycans (HSPG). In the present study, we report the binding kinetics and affinity of heparin interacting with different growth factors, including fibroblast growth factor (FGF) 2,7,10, hepatocyte growth factor (HGF) and transforming growth factor (TGF β-1), using a heparin chip. Surface plasmon resonance studies revealed that all the tested growth factors bind to heparin with high affinity (with KD ranging from ~0.1 to 59 nM) and all the interactions are oligosaccharide size dependent except those involving TGF β-1. These heparin-binding growth factors also interact with other glycosaminoglycans (GAGs), as well as various chemically modified heparins. Other GAGs, including heparan sulfate, chondroitin sulfates A, B, C, D, E and keratan sulfate, showed different inhibition activities for the growth factor-heparin interactions. FGF2, FGF7, FGF10 and HGF bind heparin but the 2-O-sulfo and 6-O-sulfo groups on heparin have less impact on these interactions than do the N-sulfo groups. All the three sulfo groups (N-, 2-O and 6-O) on heparin are important for TGFβ-1-heparin interaction.

scholarly journals Heparan Sulfate Acts as a Bone Morphogenetic Protein Coreceptor by Facilitating Ligand-induced Receptor Hetero-oligomerization

2010 ◽  
Vol 21 (22) ◽  
pp. 4028-4041 ◽  
Author(s):  
Wan-Jong Kuo ◽  
Michelle A. Digman ◽  
Arthur D. Lander
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Bone Morphogenetic Proteins ◽  
Growth Factor Receptor ◽  
In Vivo Studies ◽  
Type I ◽  
Receptor Complexes

Cell surface heparan sulfate (HS) not only binds several major classes of growth factors but also sometimes potentiates their activities—an effect usually termed “coreception.” A view that coreception is due to the stabilization of growth factor–receptor interactions has emerged primarily from studies of the fibroblast growth factors (FGFs). Recent in vivo studies have strongly suggested that HS also plays an important role in regulating signaling by the bone morphogenetic proteins (BMPs). Here, we provide evidence that the mechanism of coreception for BMPs is markedly different from that established for FGFs. First, we demonstrate a direct, stimulatory role for cell surface HS in the immediate signaling activities of BMP2 and BMP4, and we provide evidence that HS–BMP interactions are required for this effect. Next, using several independent assays of ligand binding and receptor assembly, including coimmunoprecipitation, cross-linking, and fluorescence fluctuation microscopy, we show that HS does not affect BMP binding to type I receptor subunits but instead enhances the subsequent recruitment of type II receptor subunits to BMP-type I receptor complexes. This suggests a view of HS as a catalyst of the formation of signaling complexes, rather than as a stabilizer of growth factor binding.

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