Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice.
Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice.
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DOI：
10.1038/ncomms15162
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发表时间：
2017-05-02
影响因子：
16.6
通讯作者：
Dimmeler S
中科院分区：
文献类型：
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作者：
Lucas T;Schäfer F;Müller P;Eming SA;Heckel A;Dimmeler S
microRNA（miRs）是一类转录后调控基因表达的非编码小RNA。通过反义RNA（antimiR）抑制miR可能是许多疾病的治疗选择，但全身性抑制可能具有不利影响。在这里，我们表明，光激活antimiRs有效地和局部限制目标miR在体内的活动。我们使用antimiR-92 a并在糖尿病伤口愈合中建立了治疗益处。AntimiR-92 a被对光不稳定的保护基团修饰，所谓的“笼”。辐射激活皮内注射的笼状antimiR-92 a，而基本上不影响其他器官中的miR-92 a表达。光激活笼中的antimiR-92 a可改善糖尿病小鼠的愈合，其程度与常规antimiR相似，并可解除miR-92 a靶向Itga 5和Sirt 1的抑制，从而调节伤口细胞增殖和血管生成。这些数据表明，光可用于在体内局部活化治疗活性antimiR。使用antimiR抑制microRNA是许多疾病的潜在治疗选择，但全身性抑制可能导致不良反应。在这里，作者开发了针对miR-92 a的光激活antimiRs，并在糖尿病小鼠的皮肤中显示出局部抑制作用和改善的伤口愈合。
MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. We use an antimiR-92a and establish a therapeutic benefit in diabetic wound healing. AntimiR-92a is modified with photolabile protecting groups, so called ‘cages'. Irradiation activates intradermally injected caged antimiR-92a without substantially affecting miR-92a expression in other organs. Light activation of caged antimiR-92a improves healing in diabetic mice to a similar extent as conventional antimiRs and derepresses the miR-92a targets Itga5 and Sirt1, thereby regulating wound cell proliferation and angiogenesis. These data show that light can be used to locally activate therapeutically active antimiRs in vivo. Inhibition of microRNAs using antimiRs is a potential therapeutic option for a number of diseases, but systemic inhibition may cause adverse effects. Here the authors develop light-activated antimiRs directed against miR-92a, and show localized inhibition in the skin and improved wound healing in diabetic mice.