title: Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.
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.
authors.affiliation: Hope Heart Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Harten
authors.forename: Rima S
authors.initials: RS
authors.lastname: Zahr
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lemire
authors.forename: Jason T
authors.initials: JT
authors.lastname: Machan
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Doiron
authors.forename: Adam S
authors.initials: AS
authors.lastname: Curatolo
authors.forename: Frank G
authors.initials: FG
authors.lastname: Rothman
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
mesh_terms: D000375:Aging / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D011371:Progeria / Q000201:enzymology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000166:cytology
chemical_list: D019278:Matrix Metalloproteinase 3