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Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice

Author

Listed:
  • Tina Lucas

    (Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt
    German Center for Cardiovascular Research (DZHK))

  • Florian Schäfer

    (Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt)

  • Patricia Müller

    (Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt)

  • Sabine A. Eming

    (University of Cologne
    Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Alexander Heckel

    (Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt)

  • Stefanie Dimmeler

    (Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt
    German Center for Cardiovascular Research (DZHK))

Abstract

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.

Suggested Citation

  • Tina Lucas & Florian Schäfer & Patricia Müller & Sabine A. Eming & Alexander Heckel & Stefanie Dimmeler, 2017. "Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15162
    DOI: 10.1038/ncomms15162
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