scholarly journals Induction of Urokinase-type Plasminogen Activator by Fibroblast Growth Factor (FGF)-2 Is Dependent on Expression of FGF Receptors and Does Not Require Activation of Phospholipase Cγ1

1996 ◽  
Vol 271 (49) ◽  
pp. 31154-31159 ◽  
Author(s):  
Monireh Roghani ◽  
Moosa Mohammadi ◽  
Joseph Schlessinger ◽  
David Moscatelli
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Fibroblast Growth ◽  
Type Plasminogen Activator ◽  
Phospholipase Cγ1 ◽  
Urokinase Type Plasminogen Activator

scholarly journals A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction distinguishes urokinase-type plasminogen activator induction from mitogenicity in endothelial cells.

1996 ◽  
Vol 7 (3) ◽  
pp. 369-381 ◽  
Author(s):  
M Rusnati ◽  
P Dell'Era ◽  
C Urbinati ◽  
E Tanghetti ◽  
M L Massardi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Soluble Form ◽  
Receptor Interaction ◽  
Fibroblast Growth ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase-type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM 7373 cells. In the present paper we investigated the role of the interaction of FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up-regulation in these cells. The results show that FGF-2 antagonists suramin, protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that affect growth factor binding to cell surface receptors and mitogenic activity. In contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2, indicating that FGFR and its TK activity are essential in mediating uPA induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1 mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic response. Liposome-encapsulated FGF-2 showed a limited but significant capacity, relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees C and to be internalized within the cell. uPA up-regulation by liposome-encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating that the activity of liposome-delivered FGF-2 is mediated by an extracellular action of the growth factor. Taken together, the data indicate that a distinct interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different from the one that leads to mitogenicity, is responsible for the uPA-inducing activity of the growth factor.

scholarly journals Enhanced Angiogenic Capacity and Urokinase-Type Plasminogen Activator Expression by Endothelial Cells Isolated from Human Endometrium

2001 ◽  
Vol 86 (7) ◽  
pp. 3359-3367 ◽  
Author(s):  
Pieter Koolwijk ◽  
Kitty Kapiteijn ◽  
Bibi Molenaar ◽  
Erik van Spronsen ◽  
Bea van der Vecht ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Microvascular Endothelial Cells ◽  
Fibroblast Growth ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Microvascular Endothelial

The endometrium is a tissue unique for its cyclic destruction and rapid regeneration of blood vessels. Angiogenesis, indispensable for the regeneration process, provides a richly vascularized, receptive endometrium fundamental for implantation, placentation, and embryogenesis. Human endometrial microvascular endothelial cells (hEMVEC) were isolated to better understand the properties and angiogenic behavior of these cells. Unlike human foreskin microvascular endothelial cells (hFMVEC), which proliferated better upon stimulation by basic fibroblast growth factor, hEMVEC were much more sensitive to vascular endothelial growth factor A (VEGF-A) stimulation, probably due to enhanced VEGF receptor 2 expression. In addition, hEMVEC displayed an enhanced expression of the urokinase-type plasminogen activator (u-PA) compared with hFMVEC. No differences were found in tissue-type PA, PA inhibitor-1, and u-PA receptor expression. The high expression of u-PA by hEMVEC was also found in tissue sections. hEMVEC formed capillary-like structures when cultured in 20% human serum on top of three-dimensional fibrin matrices, and VEGF-A or basic fibroblast growth factor increased this tube formation. This is in contrast with hFMVEC, which formed tubes only after simultaneous stimulation by a growth factor and tumor necrosis factor-α. The high basal level of u-PA contributes to and may explain the higher angiogenic properties of hEMVEC (in vitro).

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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