Document Detail

Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.
MedLine Citation:
PMID:  21852285     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-17
Journal Detail:
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:
Created Date:  2011-10-17     Completed Date:  2012-01-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9502837     Medline TA:  J Gerontol A Biol Sci Med Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1201-7     Citation Subset:  AIM; IM    
Hope Heart Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
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MeSH Terms
Aging / metabolism*
Blotting, Western
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Fibroblasts / enzymology*
Gene Expression Regulation / physiology
Matrix Metalloproteinase 3 / metabolism*
Progeria / enzymology*
Real-Time Polymerase Chain Reaction
Skin / cytology
Grant Support
Reg. No./Substance:
EC Metalloproteinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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