MicroRNA-132 with therapeutic potential in chronic wounds.

Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search towards more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared to normal skin wounds, and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared to 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 revealed that several inflammation-related signaling pathways, e.g. NF-κB, NOD-like receptor, Toll-like receptor, TNF signaling pathways, were the top ones regulated by miR-132 in vivo. Moreover, we applied topically liposome-formulated miR-132 mimics mixed with pluronic F-127 gel on human ex vivo skin wounds, which treatment promoted re-epithelialization. Together, our study demonstrated the therapeutic potential of miR-132 in chronic wounds, which warrants further evaluation in controlled clinical trials.