The journal of gene medicine 2018 04 15() e3022 doi 10.1002/jgm.3022
The cellular and molecular mechanisms for aged-associated delay of cutaneous wound healing are still not well understood. Our previous results show that miR-21 plays key roles during skin wound healing. We presumed that dysregulation of miR-21 may involve in aged-associated defects in wound healing and miR-21 may be one potential therapeutic target to ameliorate wound defects in elderly subjects.
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. And the expression patterns of miR-21 during wound healing in both young and aged mice were assessed by ISH. The effects of topical miR-21 overexpression on wound healing of aged mice were estimated by both wound closure quantification and histological analyses.
Aged miR-21 knock-in female mice showed significantly improved wound healing comparing with the wild-type counterparts featured with mature granulation tissue, smaller wound width and thinner epidermis. The expression patterns of miR-21 showed miR-21 levels were insufficient in repairing granulation tissue in aged mice. Intradermal injecting miR-21 plasmid around wounds could upregulate miR-21 levels during wound healing and ameliorate aged-associated skin wound defects.
Our results reveal that upregulating miR-21 levels could improve wound repair in aged mice, which suggests that a therapeutic strategy targeting miR-21 expression in aged-associated wound healing may be feasible.