Activator protein-1 (AP-1), which is a transcription factor, is implicated in the
transcriptional regulation of a wide range of genes that participate in cell proliferation
and extracellular matrix production. This investigation was performed to test the
hypothesis that transfection of cardiac fibroblasts (CFs) with sufficient amounts
of decoy oligodeoxynucleotides (ODNs) containing the AP-1-binding site would result
in binding to the transfactor AP-1, which would thereby prevent CF proliferation and
matrix metalloproteinase (MMP) expression. CFs from Sprague-Dawley rat hearts were
cultured and exposed to different concentrations of xanthine + xanthine oxidase (XXO)
and AP-1 decoy ODNs. MMP expression was assayed after oxidative stress and transfection
with AP-1 decoy ODNs by real-time quantitative polymerase chain reaction and Western
blot. Cell growth was determined by the cell count. XXO significantly increased the
DNA-binding activity of AP-1 in a dose-dependent manner. We found that transfection
with AP-1 decoy ODNs strongly inhibited XXO-induced CF proliferation and MMP gene
expression in vitro. Taken together, our data demonstrate that AP-1 is a key transcription factor that
mediates CF proliferation and MMP synthesis under oxidative stress. Transfection with
AP-1 decoy ODNs may be a novel strategy to inhibit CF proliferation and MMP synthesis.
Abbreviations:
AP-1 (activator protein-1), CF (cardiac fibroblast), DMEM (Dulbecco's modified eagle's medium), DTT (dithiothreitol), EDTA (ethylenediaminetetraacetic acid), EMSA (electrophoretic mobility shift assay), ERK (extracellular signal-regulated kinase), FBS (fetal bovine serum), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), IgG (immunoglobulin G), JNK (c-Jun N-terminal kinase), MAPK (mitogen-activated protein kinase), M-decoy ODN (mutated AP-1 decoy ODN), MI (myocardial infarction), MMP (matrix metalloproteinase), mRNA (messenger RNA), ODN (oligodeoxynucleotide), PCR (polymerase chain reaction), PMSF (phenylmethylsulphonyl fluoride), PS (penicillin-streptomycin), XXO (xanthine + xanthine oxidase)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 08, 2008
Accepted:
November 8,
2008
Received in revised form:
November 7,
2008
Received:
August 21,
2008
Footnotes
Supported by Grant NSFC 30770899 from the National Natural Science Foundation of China.
Identification
Copyright
© 2009 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
