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Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function
Author(s) -
Fujiwara Toshihiro,
Duscher Dominik,
Rustad Kristine C.,
Kosaraju Revanth,
Rodrigues Melanie,
Whittam Alexander J.,
Januszyk Michael,
Maan Zeshaan N.,
Gurtner Geoffrey C.
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12909
Subject(s) - wound healing , oxidative stress , fibroblast , superoxide dismutase , reactive oxygen species , extracellular , neovascularization , microbiology and biotechnology , biology , immunology , cancer research , endocrinology , angiogenesis , biochemistry , in vitro
Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species ( ROS ) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra‐cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ec SOD / SOD 3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS . Here, we demonstrate that reduced SOD 3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD 3 KO and aged fibroblasts both display reduced production of TGF ‐ β 1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS , decreased SOD 3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD 3 as a possible target to correct age‐related cellular dysfunction in wound healing.