MiR‐21 ameliorates age‐associated skin wound healing defects in mice

Abstract Background The cellular and molecular mechanisms responsible for the age‐associated delay of cutaneous wound healing are still not well understood. Previous studies have shown that miR‐21 plays key roles during skin wound healing. We presumed that dysregulation of miR‐21 may be involved in age‐associated defects in wound healing and that miR‐21 may be one potential therapeutic target by which to ameliorate wound defects in elderly subjects. Methods Circular full thickness excisional wounds were made on the dorsal skin of young (2‐month‐old) and aged (12‐month‐old) female mice. The wound healing rates were quantified and compared between wild‐type and miR‐21 knock‐in mice. Both histologic and morphometric analyses of the wounds were evaluated. Furthermore, the expression patterns of miR‐21 during wound healing in both young and aged mice were assessed by in situ hybridization. The effects of topical miR‐21 overexpression on wound healing in aged mice were estimated by both wound closure quantification and histological analyses. Results Aged miR‐21 knock‐in female mice showed significantly improved wound healing compared to their wild‐type counterparts with respect to mature granulation tissue, smaller wound width and thinner epidermis. The expression patterns of miR‐21 showed that miR‐21 levels were insufficient for repairing granulation tissue in aged mice. Intradermal injection of miR‐21 plasmid around wounds could upregulate miR‐21 levels during wound healing and ameliorate age‐associated skin wound defects. Conclusions The results of the present study reveal that the upregulation of miR‐21 levels could improve wound repair in aged mice, which suggests that a therapeutic strategy targeting miR‐21 expression in age‐associated wound healing may be feasible.