Identification and analysis of molecules involved in the susceptibility of melanocytes to oxidative stress in vitiligo pathogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Inoue Shintarou 岐阜薬科大学, 薬学部, 特任教授 (00793853)
• Co-Investigator(Kenkyū-buntansha): 水谷 有紀子 岐阜薬科大学, 薬学部, 特任准教授 (30396296)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 白斑 / ケラチノサイト / GPNMB / 酸化ストレス / 分化 / 細胞接着 / 発がん

Outline of Final Research Achievements

Environmental factors such as infections and oxidative stress (OS) are involved in the pathogenesis and maintenance of vitiligo (VL). We have reported that the membrane protein GPNMB (Glycoprotein nonmetastatic melanoma protein B) expression is lost in the basal layer keratinocytes (KC) of VL lesions and are downregulated by IFN-γ. In this study, we investigated the physiological role of GPNMB in KC and its involvement in VL pathogenesis and maintenance of the disease state. As a result, this study showed that GPNMB contributes as an OS resistance in KC and is involved in differentiation, stratum corneum maturation, cell adhesion, and regulation of carcinogenesis-related gene expression, suggesting that GPNMB contribute to melanocyte floating and carcinogenesis risk.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

皮膚の色素細胞が消失し白斑形成が起きる後天性の自己免疫疾患、尋常性白斑の発症と病態維持には、酸化ストレスなどの環境要因も重要である。病変部の表皮細胞ではインターフェロンγの関与により膜タンパク質GPNMBの発現が消失する。本研究では、GPNMBの生理的役割と白斑発症や病態維持への関与を検討し、GPNMBが表皮細胞の酸化ストレス抵抗性、分化・角層成熟、細胞接着、発癌関連遺伝子の発現制御等に関わることを示した。これらの結果から、GPNMBが白斑での色素細胞の浮遊化や発癌リスクの低減に関与することが示唆される。