| Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome. | |
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MedLine Citation:
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PMID: 21852285 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive segmental premature aging disease that includes scleroderma-like skin, progressive joint contracture, and atherosclerosis. Affected individuals die prematurely of heart attacks or strokes. Extracellular matrix dysregulation is implicated as a factor in disease progression. We analyzed messenger RNA and protein levels for matrix metalloproteinases (MMPs)-2,-3, and -9 in HGPS primary human dermal fibroblasts using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. MMP-3 messenger RNA and protein levels decreased significantly with increasing donor age in HGPS fibroblasts but not in controls. MMP-2 messenger RNA also showed a donor age-dependent decrease in HGPS fibroblasts, but levels of secreted protein were unchanged. MMP-9 was similar in HGPS and control cultures. The decreased MMP-3 may represent a shift in the inherent extracellular matrix-degrading proteolytic balance in favor of matrix deposition in HGPS. This metalloproteinase has the potential to serve as a biomarker of therapeutic efficacy when assessing treatments for HGPS. |
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Authors:
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Ingrid A Harten; Rima S Zahr; Joan M Lemire; Jason T Machan; Marsha A Moses; Robert J Doiron; Adam S Curatolo; Frank G Rothman; Thomas N Wight; Bryan P Toole; Leslie B Gordon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-17 |
Journal Detail:
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Title: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 66 ISSN: 1758-535X ISO Abbreviation: J. Gerontol. A Biol. Sci. Med. Sci. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-17 Completed Date: 2012-01-18 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 9502837 Medline TA: J Gerontol A Biol Sci Med Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1201-7 Citation Subset: AIM; IM |
Affiliation:
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Hope Heart Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism* Blotting, Western Cells, Cultured Enzyme-Linked Immunosorbent Assay Fibroblasts / enzymology* Gene Expression Regulation / physiology Humans Matrix Metalloproteinase 3 / metabolism* Progeria / enzymology* Real-Time Polymerase Chain Reaction Skin / cytology |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA045548/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.4.24.17/Matrix Metalloproteinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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