| Involvement of matrix metalloproteinases in the adipose conversion of 3T3-L1 preadipocytes. | |
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MedLine Citation:
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PMID: 12049638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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When mouse 3T3-L1 preadipocytes are induced to differentiate into adipocytes, they change from an extended fibroblast-like morphology to a rounded one. This change most likely occurs through extracellular matrix remodelling, a process known to be mediated in part by matrix metalloproteinases (MMPs). In this study, we have shown by semi-quantitative reverse transcriptase-PCR, zymographic and immunoblot analysis that MMP-2, MMP-9 and membrane type 1 (MT1)-MMP are regulated during adipose conversion. To assess the importance of MMPs for adipocytic differentiation we have used MMP-specific inhibitors as well as neutralizing antibodies. Treatment of 3T3-L1 preadipocytes with the broad MMP inhibitor Ilomastat or the more restricted MMP-2 Inhibitor I prevented their differentiation into adipocytes in a dose-dependent manner, as evidenced by absence of triglyceride accumulation. Inhibitor treatment prevented the fibronectin-network degradation, as well as the induction of the genes for peroxisome-proliferator-activated receptor gamma and adipsin, two adipocyte phenotype markers. Inhibitor treatment was effective when applied during the early stages of adipocytic conversion, whereas inhibitor treatment during later stages had little effect. Inhibitor treatment did not inhibit clonal mitotic expansion; nor did it affect the expression pattern of the adipogenic transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) or its nuclear translocation. It did, however, markedly reduce C/EBPbeta DNA-binding capacity. Taken together, these results suggest that MMPs, and notably MMP-2 and MMP-9, may be necessary mediators of adipocytic differentiation of 3T3-L1 cells. |
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Authors:
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Gilles Croissandeau; Michel Chrétien; Majambu Mbikay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 364 ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-06-06 Completed Date: 2002-08-15 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 739-46 Citation Subset: IM |
Affiliation:
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Diseases of Aging Program, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario K1Y 4K9, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Adipocytes / cytology*, enzymology Animals Antibodies / pharmacology CCAAT-Enhancer-Binding Protein-beta / metabolism Cell Differentiation / drug effects Indoles / pharmacology Kinetics Matrix Metalloproteinase 14 Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Matrix Metalloproteinases / metabolism* Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases / metabolism Mice Protease Inhibitors / pharmacology Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/CCAAT-Enhancer-Binding Protein-beta; 0/Indoles; 0/Mmp14 protein, mouse; 0/Protease Inhibitors; 142880-36-2/ilomastat; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.4.24.80/Matrix Metalloproteinase 14 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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