Tags

Type your tag names separated by a space and hit enter

Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cells.
J Thromb Haemost. 2004 Sep; 2(9):1629-36.JT

Abstract

Endothelial cell responses at sites of injury occur in a fibrin matrix and are regulated by growth factors including those of the FGF and VEGF families. The pericellular proteolytic balance is important in these responses, and FGF-2 and VEGF up-regulate endothelial cell u-PA, u-PAR and PAI-1. Because both VEGF and FGF-2 bind to fibrinogen, we have examined the capacity of fibrinogen to modulate the up-regulation of these proteins by FGF-2 and VEGF. Confluent cultures of endothelial cells were exposed to FGF-2, VEGF, and fibrinogen or to combinations of growth factors with fibrinogen. Changes in mRNA levels of u-PA, u-PAR and PAI-1 were measured by Northern blot. FGF-2 increased u-PA, u-PAR, and PAI-1 mRNA, but there was a significantly greater induction when fibrinogen was added to FGF-2 at all concentrations. The potentiation by fibrinogen was particularly evident at an FGF-2 concentration of 0.1 ng mL(-1), which resulted in non-significant change in transcript levels by itself, but significantly increased up to 2.6-fold with fibrinogen. VEGF also increased endothelial cell expression of u-PA, u-PAR and PAI-1, but this effect was not potentiated by fibrinogen. Addition of LM609, a monoclonal antibody to alphaVbeta3, significantly inhibited induction of u-PA mRNA and activity by fibrinogen-bound FGF-2 compared to FGF-2. A monoclonal antibody to FGFR1 also inhibited u-PA mRNA expression induced by fibrinogen-bound FGF-2. We conclude that fibrinogen increases the capacity of FGF-2, but not of VEGF, to up-regulate u-PA, u-PAR, and PAI-1 in endothelial cells and that fibrinogen-bound FGF-2 requires alphaVbeta3 binding to up-regulate endothelial cell u-PA.

Authors+Show Affiliations

Sahni A
Department of Medicine, Hematology/Oncology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Abha_Sahni@urmc.rochester.edu
Sahni SK
No affiliation info available
Simpson-Haidaris PJ
No affiliation info available
Francis CW
No affiliation info available

MeSH

Base SequenceCells, CulturedDNA, ComplementaryEndothelium, VascularFibrinogenFibroblast Growth Factor 2Gene ExpressionHumansPlasminogen Activator Inhibitor 1Protein BindingRNA, MessengerReceptors, Cell SurfaceReceptors, Urokinase Plasminogen ActivatorRecombinant ProteinsUrokinase-Type Plasminogen ActivatorVascular Endothelial Growth Factor A

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15333041

Citation

Sahni, A, et al. "Fibrinogen Binding Potentiates FGF-2 but Not VEGF Induced Expression of u-PA, u-PAR, and PAI-1 in Endothelial Cells." Journal of Thrombosis and Haemostasis : JTH, vol. 2, no. 9, 2004, pp. 1629-36.
Sahni A, Sahni SK, Simpson-Haidaris PJ, et al. Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cells. J Thromb Haemost. 2004;2(9):1629-36.
Sahni, A., Sahni, S. K., Simpson-Haidaris, P. J., & Francis, C. W. (2004). Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cells. Journal of Thrombosis and Haemostasis : JTH, 2(9), 1629-36.
Sahni A, et al. Fibrinogen Binding Potentiates FGF-2 but Not VEGF Induced Expression of u-PA, u-PAR, and PAI-1 in Endothelial Cells. J Thromb Haemost. 2004;2(9):1629-36. PubMed PMID: 15333041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cells. AU - Sahni,A, AU - Sahni,S K, AU - Simpson-Haidaris,P J, AU - Francis,C W, PY - 2004/8/31/pubmed PY - 2005/2/16/medline PY - 2004/8/31/entrez SP - 1629 EP - 36 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 2 IS - 9 N2 - Endothelial cell responses at sites of injury occur in a fibrin matrix and are regulated by growth factors including those of the FGF and VEGF families. The pericellular proteolytic balance is important in these responses, and FGF-2 and VEGF up-regulate endothelial cell u-PA, u-PAR and PAI-1. Because both VEGF and FGF-2 bind to fibrinogen, we have examined the capacity of fibrinogen to modulate the up-regulation of these proteins by FGF-2 and VEGF. Confluent cultures of endothelial cells were exposed to FGF-2, VEGF, and fibrinogen or to combinations of growth factors with fibrinogen. Changes in mRNA levels of u-PA, u-PAR and PAI-1 were measured by Northern blot. FGF-2 increased u-PA, u-PAR, and PAI-1 mRNA, but there was a significantly greater induction when fibrinogen was added to FGF-2 at all concentrations. The potentiation by fibrinogen was particularly evident at an FGF-2 concentration of 0.1 ng mL(-1), which resulted in non-significant change in transcript levels by itself, but significantly increased up to 2.6-fold with fibrinogen. VEGF also increased endothelial cell expression of u-PA, u-PAR and PAI-1, but this effect was not potentiated by fibrinogen. Addition of LM609, a monoclonal antibody to alphaVbeta3, significantly inhibited induction of u-PA mRNA and activity by fibrinogen-bound FGF-2 compared to FGF-2. A monoclonal antibody to FGFR1 also inhibited u-PA mRNA expression induced by fibrinogen-bound FGF-2. We conclude that fibrinogen increases the capacity of FGF-2, but not of VEGF, to up-regulate u-PA, u-PAR, and PAI-1 in endothelial cells and that fibrinogen-bound FGF-2 requires alphaVbeta3 binding to up-regulate endothelial cell u-PA. SN - 1538-7933 UR - https://www.unboundmedicine.com/medline/citation/15333041/Fibrinogen_binding_potentiates_FGF_2_but_not_VEGF_induced_expression_of_u_PA_u_PAR_and_PAI_1_in_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -