MicroRNA-132 with Therapeutic Potential in Chronic Wounds

• Published in: Journal of investigative dermatology Vol. 137; no. 12; pp. 2630 - 2638
• Main Authors: Li, Xi, Li, Dongqing, Wang, Aoxue, Chu, Tongbin, Lohcharoenkal, Warangkana, Zheng, Xiaowei, Grünler, Jacob, Narayanan, Sampath, Eliasson, Sofie, Herter, Eva K., Wang, Yang, Ma, Yannan, Ehrström, Marcus, Eidsmo, Liv, Kasper, Maria, Pivarcsi, Andor, Sonkoly, Enikö, Catrina, Sergiu-Bogdan, Ståhle, Mona, Xu Landén, Ning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2017
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetic Foot - metabolism; Down-Regulation; Female; Gene Expression Regulation; Humans; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Transcriptome; Wound Healing; DFU; miR; qRT-PCR; db/db mouse
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1016/j.jid.2017.08.003

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-κB, 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.