| Autocrine expression of osteopontin contributes to PDGF-mediated arterial smooth muscle cell migration. | |
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MedLine Citation:
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PMID: 17574222 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Migration of smooth muscle cells (SMCs) from the media to the intima of arteries is involved in intimal thickening. The platelet-derived growth factor (PDGF) BB is recognized as a major migratory factor for arterial SMCs both in vitro and during neointima formation. Since PDGF acts in synergy with the matrix protein osteopontin (OPN) and also induces its expression, the present study was conceived to explore the role of the OPN produced in an autocrine fashion by PDGF-stimulated SMCs in the migration process and to define regulatory mechanisms of OPN expression. METHODS AND RESULTS: PDGF stimulation of quiescent rat aortic SMCs induced their migration (transfilter assays) and the increase of OPN expression (mRNA and protein assays). Blockade of either OPN expression by a specific short interference RNA (siRNA) or of its function by a blocking antibody decreased the PDGF-stimulated migration by about 70%, demonstrating that autocrine production and excretion of OPN are integral to the PDGF-induced SMC migration. In parallel, SMC stimulation by PDGF also activated the transcription factor CREB essentially through mitogen-activated protein kinase (MAPK) 1/2 and protein kinase A (PKA) pathways. Inhibition of either CREB expression (via siRNA) or function (via dominant-negative CREB) decreased both PDGF-induced SMC migration and OPN expression. SMC transfection with OPN promoter reporter constructs demonstrated that PDGF-induced OPN transcription is mediated by CREB binding to two functional sites of the OPN promoter: a CRE site located at -1403 and an AP-1 site located at -76. CONCLUSION: The present study demonstrates that the autocrine expression of OPN plays a major role in PDGF-induced SMC migration. It further shows that the transcription factor CREB, activated in PDGF-stimulated SMCs, plays a key role in PDGF-induced SMC migration, probably by regulating OPN expression. |
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Authors:
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Sandra Jalvy; Marie-Ange Renault; Laetitia Lam Shang Leen; Isabelle Belloc; Jacques Bonnet; Alain-Pierre Gadeau; Claude Desgranges |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-24 |
Journal Detail:
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Title: Cardiovascular research Volume: 75 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-20 Completed Date: 2007-11-27 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 738-47 Citation Subset: IM |
Affiliation:
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INSERM, U441, Pessac, F-33600, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / metabolism, pathology Autocrine Communication / physiology* Calcinosis / metabolism Cell Movement / physiology Cells, Cultured Cyclic AMP Response Element-Binding Protein / analysis, genetics, metabolism Cyclic AMP-Dependent Protein Kinases / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism Myocytes, Smooth Muscle / metabolism*, pathology* Osteopontin / analysis, genetics, physiology* Platelet-Derived Growth Factor / metabolism*, pharmacology RNA Interference RNA, Messenger / analysis RNA, Small Interfering / pharmacology Rats Rats, Wistar Stimulation, Chemical Transcription, Genetic / drug effects Transfection / methods Tunica Intima / pathology* |
| Chemical | |
Reg. No./Substance:
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0/Cyclic AMP Response Element-Binding Protein; 0/Platelet-Derived Growth Factor; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/platelet-derived growth factor BB; 106441-73-0/Osteopontin; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
Comment In:
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Cardiovasc Res. 2007 Sep 1;75(4):634-5
[PMID:
17643404
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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