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.

THE OPPOSING OF BASIC FIBROBLAST GROWTH FACTOR AND TRANSFORMING GROWTH FACTOR BETA ON THE REGULATION OF PLASMINOGEN ACTIVATOR ACTIVITY IN CAPILLARY ENDOTHELIAL CELLS

1987 ◽  
Author(s):  
O Saksela ◽  
D Moscatelli ◽  
D B Rifkin
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Capillary Endothelial Cells ◽  
Growth Factor Beta ◽  
Pai 1

Basic fibroblast growth factor (bFGF), a potent inducer of angio-genesis in vivo, stimulates the production of both the cell-associated and the secreted forms of urokinase-and tissue-type plasminogen activators (PA) in cultured bovine capillary endothelial cells. This stimulation was counteracted by picogram amounts of transforming growth factor beta The stimulatory effect of bFGF was not completely abolished by increasing the amount of TGFb However, the inhibition by TGFb was greatly enhanced if the cells were pretreated for 1-3 hours with TGFb before addition of bFGF, and the inhibition was almost total, if the' preincubationtime with TGFb was 6 hours.Sequential chanqes of serum-containing medium prior to addition ofbFGF also blocked the PA stimulatory effect of bFGF. This inhibitory activity of serum was reduced by incubation of the serum with anti-TGFb-IgG. After pro-longed incubation of cultures treated simultaneously with bFGF' and TGFb, the inhibitory effect of the added bFGF dominated as assayed by PAlevels. TGFbdid not alter the receptor binding of labeled bFGF, nor did a 6 hour pretreatment with TGFb reducethe amount of bound bFGF. The major difference between effects by bFGF and TGFb was thatwhile bFGF effectively enhanced PA-activi-ty expressed by the cells, TGF decreased the amounts of both cell-associated and secreted PA activity by decreasing enzyme production and proenzyme activation. Both bFGF and TGFb increased the secretion of the endothelial type 1 plasminogen activatorinhibitor (PAI 1). The highest concentration of TGFb is found in platelets, and it is known to be released during clot formation. The suppression of PA production by theendothelium by the release of TGFb shouldresult in a decrease in the fibrinolytic activity and promote clot maintenance. In addition, the rapid stimulation of high levels of PAI 1 secretion from the surrounding capillarycells by platelet released TGFb may further suppress fibrinolysis'. The reversabil it.y of theTGFb effect and domination of bFGF stimulation may be important in relation to the subsequentonset of clot lysis or angiogenesis leadino to thrombus reorganization and wound healing.

Induction of chondrogenesis: requirement for synergistic interaction of basic fibroblast growth factor and transforming growth factor-beta

Development ◽  
1994 ◽  
Vol 120 (2) ◽  
pp. 415-424 ◽  
Author(s):  
D.A. Frenz ◽  
W. Liu ◽  
J.D. Williams ◽  
V. Hatcher ◽  
V. Galinovic-Schwartz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Otic Capsule ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Growth Factor Beta

Interactions between the epithelial anlage of the developing mouse inner ear and its associated periotic mesenchyme control the differentiation of the cartilaginous otic capsule. Transforming growth factor-beta 1 (TGF-beta 1) is a naturally occurring signal peptide that is present in these tissues at times of active differentiation and morphogenesis. Previous studies have shown that TGF-beta 1 alone is not a sufficient stimulus to initiate chondrogenesis in cultured periotic mesenchyme. In this study, we provide evidence that basic fibroblast growth factor (bFGF) can elicit a specific but limited chondrogenic response in cultured periotic mesenchymal cells. We also demonstrate that simultaneous addition of bFGF and TGF-beta 1 to cultured periotic mesenchyme results in a full chondrogenic response comparable to that which occurs when periotic mesenchyme is grown in the presence of its natural inductor tissue (i.e. otic epithelium). Utilizing antibodies directed against bFGF, we show localization of endogenous bFGF in the otic epithelium in vivo and in mixed epithelial-mesenchymal cultures. Additionally, we demonstrate the presence of FGF-like activity in medium conditioned by otic epithelium. Blocking of epithelial elicited chondrogenesis by a combination of both alpha bFGF and alpha TGF-beta 1 antibodies provides further evidence of the necessity for these growth factors in the chondrogenic differentiation of periotic mesenchyme in vitro. Our results suggest a role for both bFGF and TGF-beta 1 in the regulation of chondrogenesis during otic capsule formation in situ.

Endothelial Cells Synthesize Basic Fibroblast Growth Factor and Transforming Growth Factor Beta

1988 ◽  
Vol 1 (1) ◽  
pp. 7-17 ◽  
Author(s):  
Robert L. Hannan ◽  
Stella Kourembanas ◽  
Kathleen C. Flanders ◽  
Snezna J. Rogelj ◽  
Anita B. Roberts ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Growth Factor Beta

In vitro modulation of endothelial fenestrae: opposing effects of retinoic acid and transforming growth factor beta

1988 ◽  
Vol 91 (2) ◽  
pp. 313-318
Author(s):  
T. Lombardi ◽  
R. Montesano ◽  
M.B. Furie ◽  
S.C. Silverstein ◽  
L. Orci
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Surface Density ◽  
Transforming Growth Factor ◽  
Control Cell ◽  
Tgf Beta ◽  
Growth Factor Beta

Cultured endothelial cells isolated from fenestrated capillaries express many properties characteristic of their in vivo differentiated phenotype, including the formation of a limited number of fenestrae. In this study, we have investigated whether physiological factors that control cell differentiation might regulate the surface density of fenestrae in capillary endothelial cells. We have found that treatment of the cultures with retinoic acid (10 microM) induces a more than threefold increase in the surface density of endothelial fenestrae, whereas transforming growth factor beta (TGF beta) (2 ng ml-1) causes a sevenfold decrease in the surface density of these structures. These results show that the expression of endothelial fenestrae is susceptible to bidirectional modulation by physiological signals, and suggest that retinoids and TGF beta may participate in the regulation of fenestral density of capillary endothelium in vivo.

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