Mechanisms of change in Sema3A expression in atopic dermatitis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08756
• 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: Juntendo University
• Principal Investigator: Kamata Yayoi 順天堂大学, 大学院医学研究科, 准教授 (00410035)
• Co-Investigator(Kenkyū-buntansha): 高森 建二 順天堂大学, 医学部, 特任教授 (40053144) ; 冨永 光俊 順天堂大学, 大学院医学研究科, 先任准教授 (50468592)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: セマフォリン3A / 表皮角化細胞 / アトピー性皮膚炎 / かゆみ / 表皮バリア

Outline of Final Research Achievements

In this study, we investigated the mechanisms of change in semaphorin 3A (Sema3A) expression in lesional skin of atopic dermatitis. Sema3A expression in normal human epidermal keratinocyte (NHEK) was increased by interleukin (IL)-4, IL-13, and tumor necrosis factor (TNF)-α, but was not affected by the other cytokines tested. The combination of IL-4, IL-13, IL-22, and TNF-α significantly increased Sema3A mRNA expression. Meanwhile, filaggrin (FLG) silencing in NHEK suppressed mRNA expression of Sema3A. FLG silencing suppressed the upregulation of Sema3A by the above-mentioned cytokine combination. In addition, Sema3A expression was decreased in reconstructed human epidermis after barrier disruption by application of detergent. Collectively, these results suggest that the suppression of Sema3A expression is influenced by skin barrier defects, but not by cytokines.

Free Research Field

皮膚科学、生化学

Academic Significance and Societal Importance of the Research Achievements

先行研究より、セマフォリン（Sema）3Aはアトピー性皮膚炎（AD）病態の鍵分子の一つであると考えられている。本研究では、AD病変部におけるSema3Aの発現減少要因には炎症よりも表皮バリア機能異常が関与することを明らかにした。本研究成果はSema3Aタンパク質軟膏に代わるSema3A発現調節剤の開発を加速させ、将来的にADの難治性かゆみに苦しむ国民のQuality of lifeの向上につながることが期待される。