Document Detail

Zmpste24-/- mouse model for senescent wound healing research.
MedLine Citation:
PMID:  23190830     Owner:  NLM     Status:  In-Data-Review    
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.
Parag Butala; Caroline Szpalski; Marc Soares; Edward H Davidson; Denis Knobel; Stephen M Warren
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Plastic and reconstructive surgery     Volume:  130     ISSN:  1529-4242     ISO Abbreviation:  Plast. Reconstr. Surg.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  788e-98e     Citation Subset:  AIM; IM    
New York, N.Y. From the Institute of Reconstructive Plastic Surgery Laboratory, New York University Langone Medical Center.
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