Exploring a Role for Regulatory miRNAs In Wound Healing during Ageing:Involvement of miR-200c in wound repair.
Exploring a Role for Regulatory miRNAs In Wound Healing during Ageing:Involvement of miR-200c in wound repair.
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DOI：
10.1038/s41598-017-03331-6
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发表时间：
2017-06-12
影响因子：
4.6
通讯作者：
Botchkareva NV
中科院分区：
文献类型：
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作者：
Aunin E;Broadley D;Ahmed MI;Mardaryev AN;Botchkareva NV
多种因素和条件可导致伤口愈合受损。慢性不愈合伤口在老年人中是一个常见问题。为了确定对伤口修复有负面影响的微小核糖核酸（microRNAs），对从年轻和年老小鼠收集的伤口进行了全面的微小核糖核酸图谱分析。鉴定出了在伤口闭合过程中呈现年龄依赖性表达模式的一组微小核糖核酸，包括miR - 31和miR - 200c。在年轻和年老小鼠受伤时，miR - 200家族成员的表达均显著下调，但在老年皮肤伤口愈合的早期阶段，miR - 200c会急性上调除外。在未受伤的老年皮肤（与未受伤的年轻皮肤相比）中，人类和小鼠的miR - 200c水平也被发现升高。在人离体伤口中过表达miR - 200c会延迟再上皮化，并抑制伤口上皮细胞的增殖。在体外对人和小鼠角质形成细胞中miR - 200c表达的调节显示，miR - 200c对迁移有抑制作用，但对增殖没有。抗miR - 200c在体外诱导的伤口加速闭合与控制细胞迁移的基因上调有关。因此，我们的研究确定miR - 200c是抑制受伤后皮肤修复过程中细胞迁移的关键决定因素，并且可能导致与年龄相关的伤口修复改变。
Multiple factors and conditions can lead to impaired wound healing. Chronic non-healing wounds are a common problem among the elderly. To identify microRNAs negatively impacting the wound repair, global miRNA profiling of wounds collected from young and old mice was performed. A subset of miRNAs that exhibited an age-dependent expression pattern during wound closure was identified, including miR-31 and miR-200c. The expression of miR-200 family members was markedly downregulated upon wounding in both young and aged mice, with an exception of acute upregulation of miR-200c at the early phase of wound healing in aged skin. In unwounded aged skin (versus unwounded younger skin), the level of miR-200c was also found elevated in both human and mice. Overexpression of miR-200c in human ex vivo wounds delayed re-epithelialisation and inhibited cell proliferation in the wound epithelium. Modulation of miR-200c expression in both human and mouse keratinocytes in vitro revealed inhibitory effects of miR-200c on migration, but not proliferation. Accelerated wound closure in vitro induced by anti-miR-200c was associated with upregulation of genes controlling cell migration. Thus, our study identified miR-200c as a critical determinant that inhibits cell migration during skin repair after injury and may contribute to age-associated alterations in wound repair.