Role of Mrgpr in itch associated with atopic dermatitis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Fujii Masanori 京都薬科大学, 薬学部, 准教授 (40434667)
• Co-Investigator(Kenkyū-buntansha): 大矢 進 名古屋市立大学, 大学院医学研究科, 教授 (70275147)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 痒み / アトピー性皮膚炎 / Mas関連Gタンパク質共役受容体

Outline of Final Research Achievements

Itch is the most bothersome symptom of atopic dermatitis, a common chronic skin disease. Mas-related G protein-coupled receptors (Mrgpr) are interesting therapeutic targets for intractable itch because they are reported to mediate non-histminergic itch; however, the role of Mrgpr in itch in atopic dermatitis remains unknown. In this study, we examined whether Mrgpr are involved in itch responses in mice suffering from atopic dermatitis. The major findings of the present study are as follows: 1) Ablation of MrgprA3-expressing sensory neurons by toxin receptor-mediated cell knockout suppressed mechanically induced scratching in atopic dermatitis mice. 2) Tacrolimus, a therapeutic agent for atopic dermatitis, may act directly on dorsal root ganglion cells expressing MrgprA3 to suppress their neural activation, leading to inhibition of itch sensation.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、最も一般的な皮膚疾患であるアトピー性皮膚炎の痒みと新規痒み受容体として近年注目されているMrgprとの関連性について検討した。その結果、Mrgprがアトピー性皮膚炎の痒みの治療標的となる可能性とMrgprが発現した知覚神経の抑制機構の一端を明らかにすることができた。本成果は、ヒトのアトピー性皮膚炎と類似した症状を示すモデルマウスから得られた成果であり、直ちに実際の医療に役立つものではないが、将来的にアトピー性皮膚炎の痒みに対する治療薬の開発につながる意義があると考えられる。