Comprehensive analysis for wound inflammation-related miRNAs and development of novel therapies

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05493
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Nagasaki University
• Principal Investigator: MORI Ryoichi 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30509310)
• Research Collaborator: SHIMOKAWA Isao ; KOMATSU Toshimitsu ; TANAKA Katsuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: microRNA / アンチセンスオリゴ / インターロイキン６ / 炎症 / 黄色ブドウ球菌 / 好中球 / 細胞移植 / 皮膚創傷治癒

Outline of Final Research Achievements

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response, acting by translational processing of target mRNAs. In this study, we identified inflammation-related Ago2-miRNAs, miR-223, is key for infection control. MiR-223Y/－ mice exhibit delayed sterile healing, with prolonged neutrophil activation and interleukin-6 expression, but showed considerably improved repair of S. aureus infected wounds. We also show that expression of miR-223 is regulated by C/EBPα in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/－-derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus infected wild-type wounds leads to markedly improved healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites, and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.

Free Research Field

創傷治癒学

Academic Significance and Societal Importance of the Research Achievements

本研究では、感染を具備した炎症・組織修復並びに治癒後に生じる瘢痕形成の分子メカニズムの一端を解明できた。そして、黄色ブドウ球菌感染創改善効果のあるアンチセンスオリゴ（分子標的医薬）及び細胞移植法を開発した。
本研究成果は、創傷治癒促進・瘢痕形成減弱・治癒後の精神的ストレスからの解放（いわゆる見た目の美しさ）に寄与すると考えられる。そして、世界中に存在する上記症状をもつ人々の悩み克服に繋げたい。また、医療費削減効果及び貧困地域への低価格な医療提供を介して社会貢献にも繋げる。