title: Zmpste24-/- mouse model for senescent wound healing research.
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.
authors.affiliation: New York, N.Y. From the Institute of Reconstructive Plastic Surgery Laboratory, New York University Langone Medical Center.
authors.forename: Parag
authors.initials: P
authors.lastname: Butala
authors.forename: Caroline
authors.initials: C
authors.lastname: Szpalski
authors.forename: Marc
authors.initials: M
authors.lastname: Soares
authors.forename: Edward H
authors.initials: EH
authors.lastname: Davidson
authors.forename: Denis
authors.initials: D
authors.lastname: Knobel
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Warren
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse