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.
journal_name
Plast Reconstr Surgjournal_title
Plastic and reconstructive surgeryauthors
Butala P,Szpalski C,Soares M,Davidson EH,Knobel D,Warren SMdoi
10.1097/PRS.0b013e31826d102bsubject
Has Abstractpub_date
2012-12-01 00:00:00pages
788e-798eissue
6eissn
0032-1052issn
1529-4242pii
00006534-201212000-00008journal_volume
130pub_type
杂志文章abstract:BACKGROUND:Tibial resection in children presents a unique reconstructive challenge because of technical demands, future growth potential, and repetitive loading of the lower extremity. Positioned in a tibial defect, the free fibula undergoes primary bone healing while maintaining intrinsic resistance to infection and t...
journal_title:Plastic and reconstructive surgery
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journal_title:Plastic and reconstructive surgery
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journal_title:Plastic and reconstructive surgery
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