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 Heparan sulphate glycosaminoglycans derived from endothelial cells and smooth muscle cells differentially modulate fibroblast growth factor-2 biological activity through fibroblast growth factor receptor-1

2003 ◽  
Vol 373 (1) ◽  
pp. 241-249 ◽  
Author(s):  
David BERRY ◽  
Zachary SHRIVER ◽  
Barbara NATKE ◽  
Chi-Pong KWAN ◽  
Ganesh VENKATARAMAN ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Cell Surface ◽  
Smooth Muscle Cells ◽  
Fibroblast Growth Factor ◽  
Heparan Sulphate ◽  
Cell Types ◽  
Fibroblast Growth ◽  
Fgf Signalling

Fibroblast growth factor (FGF) signalling is involved in a wide range of important biological activities with differential effects in various cell types. The activity of FGF is modulated by heparin/heparan sulphate-like glycosaminoglycans (HSGAGs), found both in the extracellular matrix and on the cell surface. HSGAGs affect FGF signalling by interacting with both the growth factor and the FGF receptor (FGFR). In this study we sought to investigate whether HSGAGs at the cell surface of bovine aortic endothelial cells (BAEC) and smooth muscle cells (SMC) can differentially modulate FGF signalling in these cell types and modulate their differential response to FGF. We find that SMC and BAEC express the same FGFR isoforms and bind FGF2 with equal affinity at the cell surface, yet FGF has a markedly higher proliferative effect on SMC than on BAEC. Isolated HSGAGs from these two cell types were found to elicit distinct patterns of proliferation in chlorate-treated cells. Furthermore, examination of focal sequences reveals that HSGAGs from SMC, but not those from BAEC, retain the sulphation pattern necessary to induce FGF2 activity. As such, the differences in FGF2-mediated proliferation can be explained by the distinct cell surface HSGAGs of the two cell types. We conclude that the focal sequences of cell surface HSGAGs from SMC and BAEC govern, at least in part, the differential activity of FGF2 on these two cell types.

scholarly journals Effect of transforming growth factor-β1 and basic fibroblast growth factor on the expression of cell surface proteoglycans in human lung fibroblasts. Enhanced glycanation and fibronectin-binding of CD44 proteoglycan, and down-regulation of glypican

1995 ◽  
Vol 310 (1) ◽  
pp. 73-81 ◽  
Author(s):  
M Romarís ◽  
A Bassols ◽  
G David
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Core Protein ◽  
Lung Fibroblasts ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Human Lung Fibroblasts

We have tested the effects of transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF) and TGF-beta 1 + bFGF on the expression of the cell surface proteoglycans (CD44, syndecans and glypican) in cultures of human lung fibroblasts (HLF). Cell surface proteoglycan expression was monitored by quantitative immunoprecipitation from metabolically labelled cells. Western and Northern blotting and evaluation of the glycanation of the proteoglycans. Stimulation of the cells with TGF-beta 1 increased the length of the chondroitin sulphate (CS) chains on CD44 (approximately 1.6-fold). bFGF, administered solely, also increased the length of the CS chains on CD44 (approximately 1.4-fold), whereas the combination of TGF-beta 1 + bFGF nearly doubled both the length and the number of the CS chains on CD44. None of these treatments lead to changes in CD44 message or core-protein expression. This enhanced glycanation of CD44 after the TGF-beta 1, bFGF and combined treatments correlated with a 2-fold increase in the affinity of the proteoglycan for fibronectin but had no influence on the binding to type I collagen. TGF-beta 1, alone or in combination with bFGF, also stimulated the CS content of syndecan-1, but none of the other syndecans was significantly affected by any of the factors or combinations tested. The expression of glypican however was significantly decreased (nearly halved) by the combination of TGF-beta 1 + bFGF, less so by TGF-beta 1 and not at all by bFGF. This decrease occurred both at the level of the message and of the core protein. These data demonstrate specific and differential effects of TGF-beta 1 and bFGF on the structure, expression and interactions of the cell surface proteoglycans of HLF.

Nitric oxide selectively amplifies FGF-2-induced mitogenesis in primary rat aortic smooth muscle cells

1994 ◽  
Vol 267 (3) ◽  
pp. H1040-H1048 ◽  
Author(s):  
A. Hassid ◽  
H. Arabshahi ◽  
T. Bourcier ◽  
G. S. Dhaunsi ◽  
C. Matthews
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Fibroblast Growth Factor ◽  
Thymidine Incorporation ◽  
Muscle Cells ◽  
Fibroblast Growth ◽  
Aortic Smooth Muscle

Fibroblast growth factor is present in blood vessels and is thought to play an important role in promoting vascular cell proliferation in vivo. In the current study, we show that three agents that activate the guanosine 3',5'-cyclic monophosphate (cGMP) system, including the nitric oxide-generating agents S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) as well as the stable cGMP analogue 8-bromo-cGMP, increased fibroblast growth factor-2 (FGF-2; basic fibroblast growth factor)-induced [3H]thymidine incorporation by severalfold in primary cultures of rat aortic smooth muscle cells. SNAP increased the efficacy, but not the potency, of FGF-2. The stimulatory effect of SNAP was selective for FGF-2-induced mitogenesis as shown by the lack of a significant effect on [3H]thymidine incorporation induced by several other growth factors. Consistent with thymidine incorporation experiments, SNAP amplified the increase of the cellular DNA content induced by FGF-2 as well as the proliferation of cells. A selective inhibitor of cGMP phosphodiesterases, zaprinast, potentiated the comitogenic effect of SNAP and its ability to increase cGMP levels, supporting the involvement of cGMP as second messenger. Consistent with previous results, and opposite to that found in primary and early subculture, SNAP decreased mitogen-induced [3H]thymidine incorporation in cells in later subculture. Because macrophage- and vascular smooth muscle-derived nitric oxide is likely to be present in relatively large concentrations after vascular injury, we speculate that endogenous nitric oxide may amplify the activity of FGF-2 in vivo.

scholarly journals The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells.

1987 ◽  
Vol 105 (2) ◽  
pp. 957-963 ◽  
Author(s):  
O Saksela ◽  
D Moscatelli ◽  
D B Rifkin
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Capillary Endothelial Cells ◽  
Growth Factor Beta

Basic fibroblast growth factor (bFGF), a potent inducer of angiogenesis in vivo, stimulates the production of both urokinase- and tissue-type plasminogen activators (PAs) in cultured bovine capillary endothelial cells. The observed increase in proteolytic activity induced by bFGF was effectively diminished by picogram amounts of transforming growth factor beta (TGF beta), but could not be abolished by increasing the amount of TGF beta. However, the inhibition by TGF beta was greatly enhanced if the cells were pretreated with TGF beta before addition of bFGF. After prolonged incubation of cultures treated simultaneously with bFGF and TGF beta, the inhibitory effect of TGF beta diminished and the stimulatory effect of the added bFGF dominated as assayed by PA levels. TGF beta did not alter the receptor binding of labeled bFGF, nor did a 6-h pretreatment with TGF beta reduce the amount of bFGF bound. The major difference between the effects of bFGF and TGF beta was that while bFGF effectively enhanced PA activity expressed by the cells, TGF beta decreased the amounts of both cell-associated and secreted PA activity by decreasing enzyme production. Both bFGF and TGF beta increased the secretion of the endothelial-type plasminogen activator inhibitor.

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