Cargando…

Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid

BACKGROUND: Tissue factor (TF), expressed in endothelial cells (ECs) and enriched in human atherosclerotic lesions, acts as a critical initiator of blood coagulation in acute coronary syndrome. Basic fibroblast growth factor (bFGF) induces the proliferation and migration of ECs and plays a role in a...

Descripción completa

Detalles Bibliográficos
Autores principales: Kaneko, Takeaki, Fujii, Satoshi, Matsumoto, Akio, Goto, Daisuke, Makita, Naomasa, Hamada, Junichi, Moriuchi, Tetsuya, Kitabatake, Akira
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC270084/
https://www.ncbi.nlm.nih.gov/pubmed/14613528
http://dx.doi.org/10.1186/1477-9560-1-6
_version_ 1782121027165224960
author Kaneko, Takeaki
Fujii, Satoshi
Matsumoto, Akio
Goto, Daisuke
Makita, Naomasa
Hamada, Junichi
Moriuchi, Tetsuya
Kitabatake, Akira
author_facet Kaneko, Takeaki
Fujii, Satoshi
Matsumoto, Akio
Goto, Daisuke
Makita, Naomasa
Hamada, Junichi
Moriuchi, Tetsuya
Kitabatake, Akira
author_sort Kaneko, Takeaki
collection PubMed
description BACKGROUND: Tissue factor (TF), expressed in endothelial cells (ECs) and enriched in human atherosclerotic lesions, acts as a critical initiator of blood coagulation in acute coronary syndrome. Basic fibroblast growth factor (bFGF) induces the proliferation and migration of ECs and plays a role in angiogenesis and restoration of endothelial integrity. As TF is implicated in angiogenesis, we studied the effect of bFGF on TF gene and protein expression. Methods: Human umbilical vein ECs (HUVECs) were exposed to bFGF. TF mRNA was assessed by Northern blot and TF protein was assessed by Western blot. TF promoter activity was assessed by transient transfection assay and transcription factor was identified by electro mobility shift assay. RESULTS: bFGF increased TF mRNA and protein expression in HUVECs. Increased TF mRNA was attenuated by inhibition of extracellular signal-regulated kinase kinase in human ECV304 cells. Transient transfection assays of the human TF promoter-luciferase construct (-786/+121 bp) demonstrated that bFGF induced transcription was dependent on the elements within the -197 to -176 bp relative to the transcription start site of the human TF gene. This region contains NF-κB like binding site. Electro mobility shift assay showed that bFGF increased nuclear translocation or DNA binding of NF-κB transcription factor to TF promoter. Nucleotide substitution to disrupt NF-κB like site reduced bFGF stimulated promoter activity. Fenofibric acid, an agonist ligand for the peroxisome proliferator activated receptor-α, reduced basal and bFGF stimulated TF expression. CONCLUSIONS: These results indicate that bFGF may increase TF production in ECs through activation of transcription at NF-κB binding site, and control coagulation in vessel walls. Fibrate can inhibit TF expression and therefore reduce the thrombogenecity of human atherosclerotic lesions.
format Text
id pubmed-270084
institution National Center for Biotechnology Information
language English
publishDate 2003
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-2700842003-11-21 Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid Kaneko, Takeaki Fujii, Satoshi Matsumoto, Akio Goto, Daisuke Makita, Naomasa Hamada, Junichi Moriuchi, Tetsuya Kitabatake, Akira Thromb J Original Basic Research BACKGROUND: Tissue factor (TF), expressed in endothelial cells (ECs) and enriched in human atherosclerotic lesions, acts as a critical initiator of blood coagulation in acute coronary syndrome. Basic fibroblast growth factor (bFGF) induces the proliferation and migration of ECs and plays a role in angiogenesis and restoration of endothelial integrity. As TF is implicated in angiogenesis, we studied the effect of bFGF on TF gene and protein expression. Methods: Human umbilical vein ECs (HUVECs) were exposed to bFGF. TF mRNA was assessed by Northern blot and TF protein was assessed by Western blot. TF promoter activity was assessed by transient transfection assay and transcription factor was identified by electro mobility shift assay. RESULTS: bFGF increased TF mRNA and protein expression in HUVECs. Increased TF mRNA was attenuated by inhibition of extracellular signal-regulated kinase kinase in human ECV304 cells. Transient transfection assays of the human TF promoter-luciferase construct (-786/+121 bp) demonstrated that bFGF induced transcription was dependent on the elements within the -197 to -176 bp relative to the transcription start site of the human TF gene. This region contains NF-κB like binding site. Electro mobility shift assay showed that bFGF increased nuclear translocation or DNA binding of NF-κB transcription factor to TF promoter. Nucleotide substitution to disrupt NF-κB like site reduced bFGF stimulated promoter activity. Fenofibric acid, an agonist ligand for the peroxisome proliferator activated receptor-α, reduced basal and bFGF stimulated TF expression. CONCLUSIONS: These results indicate that bFGF may increase TF production in ECs through activation of transcription at NF-κB binding site, and control coagulation in vessel walls. Fibrate can inhibit TF expression and therefore reduce the thrombogenecity of human atherosclerotic lesions. BioMed Central 2003-10-11 /pmc/articles/PMC270084/ /pubmed/14613528 http://dx.doi.org/10.1186/1477-9560-1-6 Text en Copyright © 2003 Kaneko et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Original Basic Research
Kaneko, Takeaki
Fujii, Satoshi
Matsumoto, Akio
Goto, Daisuke
Makita, Naomasa
Hamada, Junichi
Moriuchi, Tetsuya
Kitabatake, Akira
Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title_full Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title_fullStr Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title_full_unstemmed Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title_short Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
title_sort induction of tissue factor expression in endothelial cells by basic fibroblast growth factor and its modulation by fenofibric acid
topic Original Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC270084/
https://www.ncbi.nlm.nih.gov/pubmed/14613528
http://dx.doi.org/10.1186/1477-9560-1-6
work_keys_str_mv AT kanekotakeaki inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT fujiisatoshi inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT matsumotoakio inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT gotodaisuke inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT makitanaomasa inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT hamadajunichi inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT moriuchitetsuya inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid
AT kitabatakeakira inductionoftissuefactorexpressioninendothelialcellsbybasicfibroblastgrowthfactoranditsmodulationbyfenofibricacid