Acidic and basic fibroblast growth factors suppress transcriptional activation of tissue factor and other inflammatory genes in endothelial cells.
Tissue factor (TF) is a transmembrane receptor that serves as a cofactor for factor VIIa and initiates the extrinsic pathway of blood coagulation. Under normal physiological conditions, TF is expressed in extravascular and perivascular cells but not in vascular endothelial cells and monocytes. TF can be induced in these cells by inflammatory regulators and other stimulators, such as LPS, thrombin, oxidized lipoproteins, and certain growth factors. An earlier study showed that growing primary cultures of human umbilical vein endothelial cells (HUVECs) with endothelial cell growth supplement (ECGS) and heparin had impaired the ability of monolayers to express surface membrane TF activity after perturbation. The mechanism by which ECGS suppressed TF activity was not known. In the present study, we investigated the effect of recombinant acidic and basic fibroblast growth factors (aFGF and bFGF) on the induction of TF in a HUVEC cell line and a fibroblast cell line. Both aFGF and bFGF suppressed the phorbol myristate acetate-induced expression of TF in endothelial cells but not the serum-induced expression of TF in fibroblast cells. Diminished expression of the cell surface TF activity observed in endothelial cells grown with aFGF or bFGF was due to the accumulation of a lower number of TF mRNA transcripts. TF mRNA stability was not altered in HUVECs grown with aFGF or bFGF. Nuclear run-on experiments revealed that the transcription of TF and several other genes that play an important role in inflammation and angiogenesis was reduced in the endothelial cells that were cultured with aFGF or bFGF. The diminished expression of TF may be part of a generalized response of endothelial cells to FGF that facilitates migration of endothelial cells during angiogenesis.
Pendurthi
U R
UR
Department of Biochemistry, University of Texas Health Center at Tyler, 75703, USA. usha@uthct.edu
Williams
J T
JT
Rao
L V
LV
D002478:Cells, Cultured; D003470:Culture Media; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007700:Kinetics; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014158:Transcription, Genetic; D014471:Umbilical Veins
D003470:Culture Media; D016209:Interleukin-8; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate