Production of a Transforming Growth Factor-Beta-Like Growth Factor by RSV-Transformed Rat Cerebral Microvascular Endothelial Cells

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

The Journal of Cell Biology ◽

10.1083/jcb.105.2.957 ◽

1987 ◽

Vol 105 (2) ◽

pp. 957-963 ◽

Cited By ~ 252

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

10.1055/s-0038-1644660 ◽

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.

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