Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Military Medical University, Chongqing, China.
Department of Dermatology, Southwest Hospital, Army Military Medical University, Chongqing, China.
J Gene Med. 2018 Jun;20(6):e3022. doi: 10.1002/jgm.3022. Epub 2018 May 3.
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.
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.
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.
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.
导致皮肤创伤愈合与年龄相关的延迟的细胞和分子机制仍未得到很好的理解。先前的研究表明，miR-21 在皮肤伤口愈合过程中发挥关键作用。我们推测 miR-21 的失调可能与年龄相关的伤口愈合缺陷有关，并且 miR-21 可能是改善老年受试者伤口缺陷的潜在治疗靶点之一。
在年轻（2 个月大）和老年（12 个月大）雌性小鼠的背部皮肤上制作圆形全层切除伤口。量化并比较野生型和 miR-21 敲入小鼠之间的伤口愈合率。评估伤口的组织学和形态计量学分析。此外，通过原位杂交评估 miR-21 在年轻和老年小鼠伤口愈合过程中的表达模式。通过伤口闭合定量和组织学分析评估 miR-21 过表达对老年小鼠伤口愈合的影响。
与野生型对照相比，老年 miR-21 敲入雌性小鼠在成熟肉芽组织、较小的伤口宽度和较薄的表皮方面表现出明显改善的伤口愈合。miR-21 的表达模式表明，miR-21 水平不足以修复老年小鼠的肉芽组织。在伤口周围皮内注射 miR-21 质粒可以上调伤口愈合过程中的 miR-21 水平并改善与年龄相关的皮肤伤口缺陷。
本研究的结果表明，上调 miR-21 水平可以改善老年小鼠的伤口修复，这表明针对与年龄相关的伤口愈合中 miR-21 表达的治疗策略可能是可行的。
