Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 137, Issue 12, Pages 2630-2638Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2017.08.003
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Funding
- board of research at Karolinska Institutet
- research committee at the Karolinska hospital
- Swedish Research Council (Vetenskapsradet) [2013-03085, 2015-06246, 2016-02051]
- Ragnar Soderbergs Foundation [M31/15, M127/12]
- National Natural Science Foundation of China [81611130075]
- China Scholarship Council (CSC)
- Hedlunds Foundation
- Welander and Finsens Foundation (Hudfonden)
- Ake Wibergs Foundation
- Jeanssons Foundation
- Swedish Psoriasis Foundation
- Swedish Cancer Society
- Ming Wai Lau Centre for Reparative Medicine
- Tore Nilsons Foundation
- Lars Hiertas Foundation
- Karolinska Institutet
- Swedish Research Council [2015-06246, 2013-03085, 2016-02051] Funding Source: Swedish Research Council
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Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search toward more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared with normal skin wounds and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared with wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound edge keratinocytes and reduced inflammation. The pro-healing effect of miR-132 was further supported by global transcriptome analysis, which showed that several inflammation-related signaling pathways (e.g., NF-kappa B, NOD-like receptor, toll-like receptor, and tumor necrosis factor signaling pathways) were the top ones regulated by miR-132 in vivo. Moreover, we topically applied liposome-formulated miR-132 mimics mixed with pluronic F-127 gel on human ex vivo skin wounds, which promoted re-epithelialization. Together, our study showed the therapeutic potential of miR-132 in chronic wounds, which warrants further evaluation in controlled clinical trials.
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