| Transcription factor decoys for activator protein-1 (AP-1) inhibit oxidative stress-induced proliferation and matrix metalloproteinases in rat cardiac fibroblasts. | |
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MedLine Citation:
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PMID: 19100954 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shuanglun Xie; Ruqiong Nie; Jingfeng Wang; Fei Li; Woliang Yuan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-06 |
Journal Detail:
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Title: Translational research : the journal of laboratory and clinical medicine Volume: 153 ISSN: 1931-5244 ISO Abbreviation: Transl Res Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-22 Completed Date: 2009-03-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101280339 Medline TA: Transl Res Country: United States |
Other Details:
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Languages: eng Pagination: 17-23 Citation Subset: AIM; IM |
Affiliation:
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Department of Cardiology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510120 China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cell Proliferation Cell Survival / drug effects Cells, Cultured Dose-Response Relationship, Drug Gene Expression Regulation, Enzymologic Gene Therapy / methods* Matrix Metalloproteinase 13 / genetics* Matrix Metalloproteinase 9 / genetics* Myocytes, Cardiac / metabolism* Oligodeoxyribonucleotides / genetics* Oxidative Stress / genetics Rats Transcription Factor AP-1 / genetics*, metabolism Transfection Xanthine / pharmacology Xanthine Oxidase / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Oligodeoxyribonucleotides; 0/Transcription Factor AP-1; 69-89-6/Xanthine; EC 1.17.3.2/Xanthine Oxidase; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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