Zmpste24- mouse model for senescent wound healing research

Parag Butala, Caroline Szpalski, Marc Soares, Edward H. Davidson, Denis Knobel, Stephen M. Warren

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)788e-798e
JournalPlastic and reconstructive surgery
Volume130
Issue number6
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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