Developing new Drug -the effects of DNase suppressing NETs and biofilm formation-

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16914
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: YAMAGUCHI Kenji 東北大学, 医学系研究科, 非常勤講師 (70897892)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: バイオフィルム / 創傷治癒 / 好中球NETs / DNAse / 慢性創傷

Outline of Final Research Achievements

Biofilm formation due to bacterial colonization is said to be a factor in the chronicity of chronic wounds. It has been suggested that inflammation-inducing neutrophils and NETs released by neutrophils may be involved in biofilm formation. In this study, we analyzed the mechanism of biofilm formation, the usefulnes of DNase, and whether DNase can lead to further novel therapies. Intraperitoneal administration of DNase to mice treated with α-mannan, a fungal cell wall, as a model of intractable ulcers was shown to promote wound healing. Similar results were obtained in mice with acute wounds, indicating that inhibition of NETs by DNase promotes wound healing and suggests its potential as a therapeutic agent.

Free Research Field

創傷治癒

Academic Significance and Societal Importance of the Research Achievements

慢性創傷や難治性潰瘍に対する有効な治療選択肢が不足している現在、新たな治療薬を産出することは患者はもちろん、医療者や医療経済的負担の軽減にもつながる。本研究成果が、特に難治性潰瘍の創傷治癒を誘導する新たな治療薬の開発の一助となれば、外科手術やカテーテル治療、投薬治療に加えて新たな集学的治療の選択肢になると期待される。また、好中球NETsが創傷治癒を阻害することを支持する内容でもあり、創傷治癒に関する研究において、C型レクチン受容体を介した反応と、好中球NETsに関わる創傷治癒メカニズムの解明にもつながると考えている。