Aging-related delayed wound healing is an issue of concern worldwide. Oxidative stress is involved in wound healing. Antioxidative enzymes have various roles in this process. PRDX4, a member of the PRDX family, is upregulated after injury. To investigate the effects of PRDX4 on aging-related wound healing, we subjected C57BL/6J (wild-type), human Prdx4‒transgenic (i.e., hPrdx4+/+), Prdx4-knockout (i.e., Prdx4-/y) mice of three age groups (young, adult, and aged) to skin wound formation. The overexpression of PRDX4 accelerated wound healing in adult and aged mice but not in young mice. Aged hPrdx4+/+ mice showed reduced oxidative stress and inflammation, lower numbers of neutrophils, increased macrophage infiltration, increased angiogenesis, and increased GF levels. The granulation tissue of adult and aged hPrdx4+/+ mice was richer in fibroblasts than that in the matched wild-type mice. PRDX4 deficiency was associated with mortality in adult and aged mice. In vitro, the overexpression of PRDX4 promoted the proliferation and migration of fibroblasts derived from adult or aged mice and made fibroblasts more resistant to the cytotoxicity of hydrogen peroxide. PRDX4 is essential for wound healing and can improve the healing process from multiple aspects, suggesting that it may be very beneficial to wound treatment, especially for the elderly.
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