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- Title
Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.
- Authors
Harten, Ingrid A; Zahr, Rima S; Lemire, Joan M; Machan, Jason T; Moses, Marsha A; Doiron, Robert J; Curatolo, Adam S; Rothman, Frank G; Wight, Thomas N; Toole, Bryan P; Gordon, Leslie B
- 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.
- Publication
The journals of gerontology. Series A, Biological sciences and medical sciences, 2011, Vol 66, Issue 11, p1201
- ISSN
1758-535X
- Publication type
Journal Article
- DOI
10.1093/gerona/glr137