Molecular mechanism of inflammation-related miRNA in tissue repair and antisense oligodeoxynucleotide development

2015 Fiscal Year Final Research Report

• Project/Area Number: 24689069
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagasaki University
• Principal Investigator: MORI Ryoichi 長崎大学, 医歯薬学総合研究科(医学系), 講師 (30509310)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 皮膚創傷治癒 / miRNA / Foxo / 炎症

Outline of Final Research Achievements

I investigated function of miR-223 and Foxo1 in skin wound healing. Skin wound healing in miR-223 KO mice was delayed concomitant with altered neutrophil activation. I showed that miR-223 KO mice undergo prolonged acute inflammatory responses at wound sites due to miR-223 KO-derived neutrophils exhibiting increased hyperoxidative bursts. Intriguingly, S. aureus-infected miR-223 KO mice showed markedly faster skin wound healing than S. aureus-infected wild-type mice. Our data indicate that the molecular targeting of miR-223 may regulate the healing of bacterium-infected chronic skin wounds.
Foxo1 heterozygous mice led to accelerated skin wound healing with enhanced keratinocyte migration and reduced scarring accompanied by an attenuated inflammatory response. Transient knockdown of Foxo1 at the wound site by local delivery of antisense oligo enhanced skin wound healing. Overall, molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

Free Research Field

創傷治癒