Transcriptional and posttranscriptional regulation of urokinase-type plasminogen activator expression in endothelial cells by basic fibroblast growth factor

1995 ◽  
Vol 162 (3) ◽  
pp. 400-409 ◽  
Author(s):  
Anna Gualandris ◽  
Marco Presta
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Posttranscriptional Regulation ◽  
Fibroblast Growth ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

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 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 Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis.

1988 ◽  
Vol 107 (3) ◽  
pp. 1199-1205 ◽  
Author(s):  
Y Sato ◽  
D B Rifkin
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Basic Fibroblast Growth Factor ◽  
Cell Movement ◽  
Fibroblast Growth ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells

We have found that the spontaneous migration of bovine aortic endothelial cells from the edge of a denuded area in a confluent monolayer is dependent upon the release of endogenous basic fibroblast growth factor (bFGF). Cell movement is blocked by purified polyclonal rabbit IgG to bFGF as well as affinity purified anti-bFGF IgG and anti-bFGF F(ab')2 fragments. The inhibitory effect of the immunoglobulins is dependent upon antibody concentration, is reversible, is overcome by the addition of recombinant bFGF, and is removed by affinity chromatography of the antiserum through a column of bFGF-Sepharose. Cell movement is also reversibly inhibited by the addition of protamine sulfate and suramin; two agents reported to block bFGF binding to its receptor. The addition of recombinant bFGF to wounded monolayers accelerates the movement of cells into the denuded area. Transforming growth factor beta which has been shown to antagonize several other effects of bFGF also inhibits cell movement. The anti-bFGF IgG prevents the movement of bovine capillary endothelial cells, BHK-21, NIH 3T3, and human skin fibroblasts into a denuded area. Antibodies to bFGF, as well as suramin and protamine sulfate also suppress the basal levels of plasminogen activator and DNA synthesis in bovine aortic endothelial cells.

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