Changes in the epidermal stem cell niche during the development of diabetic foot ulcers

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09775
• 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: International University of Health and Welfare
• Principal Investigator: Matsuzaki Kyoichi 国際医療福祉大学, 医学部, 主任教授 (20278013)
• Co-Investigator(Kenkyū-buntansha): 難波 大輔 東京大学, 医科学研究所, 准教授 (10380255)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病 / 難治性潰瘍 / 表皮角化細胞 / 幹細胞 / XVII型コラーゲン

Outline of Final Research Achievements

These studies revealed that the migratory ability of epidermal keratinocyte stem cells is decreased in diabetic foot ulcers. Furthermore, studies using cultured human epidermal keratinocyte stem cell lines revealed that increased expression of TIMP-1 by EGF receptor activation and the resulting stabilization of type XVII collagen protein are essential for maintaining the migratory ability of epidermal keratinocyte stem cells. These results suggest that one of the factors contributing to the development of diabetic foot ulcers is a decrease in TIMP-1 expression due to reduced EGF receptor signaling and a decrease in the migratory ability of epidermal keratinizing stem cells due to type XVII collagen degradation.

Free Research Field

形成外科

Academic Significance and Societal Importance of the Research Achievements

EGF受容体シグナルの活性化によってヒト表皮角化幹細胞周辺のタンパク質分解酵素の活性が低下し、その結果、表皮角化幹細胞の機能が維持されることが明らかとなった。この結果は、学術的にはヒト表皮角化幹細胞ニッチの条件を明らかにしたものである。この条件を制御することで糖尿病性足潰瘍の治療法開発につながる可能性があり、本研究は大きな社会的意義を持つ。