Aging leading to delayed wound healing has become a concerned issue worldwide. Oxidative stress is involved in wound healing and antioxidative enzymes have various roles in aging-related delayed wound healing. Peroxiredoxin 4 (PRDX4), an enzyme catalyzing the detoxification of hydrogen peroxide, is a unique secreted member of the antioxidative protein PRDX family and widely expressed in various organs. In a series of previous studies, we reported that PRDX4 had important anti-oxidative anti-inflammatory roles and was important for the regulation of cell vitality, including proliferation and migration in chronic inflammatory diseases and cancer. In the previous reports, it has shown that PRDX4 is present in the skin and is upregulated after injury, but its roles in wound healing remain unknown. In this study, we subjected young (4-week-old), adult (12-week-old) and aged (1-year-old) of three ages C57BL/6J (WT) or human PRDX4 transgenic (Tg) mice to skin wound formation, to investigate effect of PRDX4 on aging-related wound healing. The overexpression of PRDX4 accelerated wound healing in adult and aged mice, but no significantly differences were observed in young mice. In aged group, reduced oxidative stress and inflammatory response, increased angiogenesis and growth factor, and more macrophages and less neutrophils infiltration were observed in Tg mice. Cell-richer granulation tissue was found in adult and aged Tg mice, compared to matched WT mice. In contrast, severely impaired wound healing and high wound-related mortality were observed in the adult and aged PRDX4-knockout 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. Our data are suggesting that PRDX4 is essential for wound healing in the elderly and can improve the healing process from various aspects.

ESDR346 - Peroxiredoxin 4 improved aging-related delayed wound healing in mice

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING