Zmpste24-/- mouse model for senescent wound healing research.
Plast Reconstr Surg
; 130(6): 788e-798e, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23190830
ABSTRACT
BACKGROUND:
The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing.METHODS:
Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry.RESULTS:
Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial.CONCLUSIONS:
The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Envelhecimento
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Metaloendopeptidases
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Modelos Animais
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Proteínas de Membrana
Tipo de estudo:
Evaluation_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Plast Reconstr Surg
Ano de publicação:
2012
Tipo de documento:
Article