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Mechanisms of improved wound healing in Murphy Roths Large (MRL) mice after skin transplantation
Author(s) -
Tolba René H.,
Schildberg Frank A.,
Decker Dorothee,
Abdullah Zeinab,
Büttner Reinhard,
Minor Thomas,
Von Ruecker Alexander
Publication year - 2010
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2010.00631.x
Subject(s) - wound healing , neovascularization , stat3 , transplantation , angiogenesis , vascular endothelial growth factor , medicine , inflammation , proinflammatory cytokine , stat protein , smad , growth factor , cancer research , immunology , transforming growth factor , phosphorylation , biology , microbiology and biotechnology , surgery , receptor , vegf receptors
Scars arise in the late phase of wound healing and are characterized by fibroplasia. Previous controversial studies have discussed the regenerative wound healing capacity of Murphy Roths Large (MRL) mice. The aim of this study was to investigate the mechanisms of improved wound healing in a skin transplantation model. Skin grafts from MRL and haplotypically identical B10.BR mice were cross‐transplanted. At day 10, B10.BR and MRL grafts on B10.BR recipients deposited collagen and showed severe apoptosis. Grafts of MRL recipients were not affected by such alterations and showed an enhanced healing progress. They were characterized by higher partial pressure of tissue oxygen, increased microcirculation, exceptionally intense neovascularization, and a blunted inflammatory response. This phenotype was accompanied by increased vascular endothelial growth factor expression, augmented by enhanced signal transducer and activator of transcription 3 (STAT3) phosphorylation. These effects were combined with a decreased STAT1 expression and phosphorylation. STAT1 pattern variation was associated with decreased Smad7 levels. Furthermore, MRL recipients showed improved stem cell recruitment to the wound area. The basic accelerated wound healing mechanism in MRL mice found in this skin transplantation model is improved engraftment; this is based on enhanced neovascularization and reduced inflammation. These effects are most likely due to higher vascular endothelial growth factor levels and changes in the STAT/Smad signal pathway, which may enhance transforming growth factor‐β signaling, reducing proinflammatory responses.