Document Detail

Zmpste24-/- mouse model for senescent wound healing research.
MedLine Citation:
PMID:  23190830     Owner:  NLM     Status:  MEDLINE    
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:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural    
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:  2013-01-28     Revised Date:  2014-10-13    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  788e-798e     Citation Subset:  AIM; IM    
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MeSH Terms
Apoptosis / genetics,  physiology
Biological Markers / metabolism
DNA Fragmentation
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
In Situ Nick-End Labeling
Membrane Proteins / deficiency*,  genetics
Metalloendopeptidases / deficiency*,  genetics
Mice, Inbred C57BL
Mice, Knockout
Models, Animal*
Real-Time Polymerase Chain Reaction
Time Factors
Wound Healing / genetics,  physiology*
Grant Support
1 U54 RR024386-01A1/RR/NCRR NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Membrane Proteins; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/Zmpste24 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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