HMGB1 and LL37-containing ointments for the treatment of diabetic foot lesions (ulcers)

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Ehime University
• Principal Investigator: Tozawa Asami 愛媛大学, 医学部附属病院, 助教(病院教員) (70635531)
• Co-Investigator(Kenkyū-buntansha): 村上 正基 愛媛大学, 医学系研究科, 特任教授 (20278302) ; 森 秀樹 愛媛大学, 医学系研究科, 講師 (60325389)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HMGB1 / 創傷治癒 / 糖尿病 / LL37 / 抗菌ペプチド

Outline of Final Research Achievements

This study aimed to develop a therapeutic agent for diabetic foot lesions (ulcers) with ointments containing HMGB1 and LL37. First, a wound-delayed model was created using (1) monolayer cultures of normal skin keratinocytes and three-dimensional epidermal cultures of dermatological bacterial colonies. Then, antimicrobial peptides expressed in skin such as LL37, HBGB1, and HMGB1-ABox were applied to the system constructed in (1), and the improvement of wound delay and the induction and suppression of inflammatory cytokines were evaluated. Next, several ointments containing skin antimicrobial peptides and HMGB1 were applied to ulcers created on the backs of diabetic and TLR3 knockout mice, and the inflammatory response to these ointments was compared. Control and LL37 alone were epithelialized on day 14, and the ointments containing the HMGB1 group did not show superior wound healing.

Free Research Field

創傷治癒

Academic Significance and Societal Importance of the Research Achievements

糖尿病患者の0.3％は足潰瘍病変をもち、一旦足潰瘍を発症した場合には難治性である。糖尿病患者の発汗低下からLL37などの抗菌ペプチドの低下により表皮角化細胞の免疫機能低下が原因であることを示し、現存する軟膏とは全く違う面からの創傷治癒を促進する軟膏を開発する予定であった。HMGB1の効果は証明できていないが、LL37は創傷治癒に関して改良すれば効果がある軟膏が作れる可能性が示された。