Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.
J Gerontol A Biol Sci Med Sci
; 66(11): 1201-7, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21852285
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Progéria
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Envelhecimento
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Metaloproteinase 3 da Matriz
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Fibroblastos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article