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Role of Mrgpr in itch associated with atopic dermatitis

Research Project

Project/Area Number 16K09000
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionKyoto 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
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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 / Mrgpr / 薬理学 / 痒みの発生・増強機序
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Eicosapentaenoic acid ethyl ester ameliorates atopic dermatitis-like symptoms in special diet-fed hairless mice, partly by restoring covalently bound ceramides in the stratum corneum2018

    • Author(s)
      Fujii Masanori、Ohyanagi Chie、Kawaguchi Naomi、Matsuda Hiroyuki、Miyamoto Yoshitaka、Ohya Susumu、Nabe Takeshi
    • Journal Title

      Experimental Dermatology

      Volume: 27 Issue: 8 Pages: 837-840

    • DOI

      10.1111/exd.13507

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of pruritogens and algogens on rostral ventromedial medullary (RVM) ON and OFF cells2018

    • Author(s)
      Taylor Follansbee, Tasuku Akiyama, Masanori Fujii, Auva Davoodi, Masaki Nagamine, Mirela Iodi Carstens, Earl Carstens
    • Journal Title

      Journal of Neurophysiology

      Volume: 120 Issue: 5 Pages: 2156-2163

    • DOI

      10.1152/jn.00208.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Barbiturates enhance itch-associated scratching in atopic dermatitis mice: A possible clue to understanding nocturnal pruritus in atopic dermatitis2018

    • Author(s)
      Fujii Masanori、Takeuchi Kaori、Umehara Yuna、Takeuchi Masafumi、Nakayama Takanori、Ohgami Sayaka、Asano Erika、Nabe Takeshi、Ohya Susumu
    • Journal Title

      European Journal of Pharmacology

      Volume: 836 Pages: 57-66

    • DOI

      10.1016/j.ejphar.2018.08.018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis of Diet-induced Atopic Dermatitis in Hairless Mice2017

    • Author(s)
      藤井正徳
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 1 Pages: 49-54

    • DOI

      10.1248/yakushi.16-00200

    • NAID

      130005180844

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-01-01
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hypomorphic mutation in the hairless gene accelerates pruritic atopic skin caused by feeding a special diet to mice2016

    • Author(s)
      Masanori Fujii, Fumiko Endo-Okuno, Asuka Iwai, Keisuke Doi, Junko Tomozawa, Shigekatsu Kohno, Naoki Inagaki, Takeshi Nabe, Susumu Ohya
    • Journal Title

      Experimental Dermatology

      Volume: in press Issue: 7 Pages: 565-567

    • DOI

      10.1111/exd.13015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 食餌誘発アトピー性皮膚炎モデルの病態解析2016

    • Author(s)
      藤井正徳
    • Journal Title

      BIO Clinica

      Volume: 31 Pages: 92-97

    • Related Report
      2016 Research-status Report
  • [Journal Article] 新しい痒み研究のマウスモデル2016

    • Author(s)
      藤井正徳
    • Journal Title

      アレルギー・免疫

      Volume: 23 Pages: 30-36

    • Related Report
      2016 Research-status Report
  • [Presentation] 慢性・重度の掻痒様行動を呈するアトピー性皮膚炎マウスモデルの病態解析2018

    • Author(s)
      中嶋雅幸,櫻井千浩,橋本みさき,松本芳樹,大矢 進,藤井正徳
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Brain allopregnanolone is involved in itch-associated scratching in atopic dermatitis mice2018

    • Author(s)
      Masanori Fujii, Sayaka Ohgami, Erika Asano, Susumu Ohya
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] STIM/Orai-mediated store operated Ca2+ entry may contribute to overproduction of TSLP in epidermal cells isolated from atopic dermatitis mice2018

    • Author(s)
      Shuhei Kobayashi, Rieko Matsui, Yumeka Yamada, Hiroaki Kito, Susumu Ohya, Masanori Fujii
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dietary induction of pruritic atopic skin in C57BL/6 mice2018

    • Author(s)
      Yuma Yasui, Hoshi Watanabe, Chihiro Sakurai, Masayuki Nakashima, Susumu Ohya, Masanori Fujii
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] タクロリムスによる痒み抑制メカニズム2018

    • Author(s)
      藤井正徳,今堀翔太,田中智之
    • Organizer
      第134回日本薬理学会近畿部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] C57BL/6マウスを用いた慢性掻痒モデルの確立2017

    • Author(s)
      安井悠真, 渡辺保志, 大矢 進, 藤井正徳
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2017
    • Related Report
      2017 Research-status Report
  • [Presentation] ヘアレスマウスにおける食餌誘発アトピー性皮膚炎の発症要因の解明-多価不飽和脂肪酸およびデンプン成分の欠乏ならびにヘアレス遺伝子低形質変異の関与-2017

    • Author(s)
      藤井正徳
    • Organizer
      第67回日本薬学会近畿支部総会・大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規アトピー性掻痒マウスモデルの開発2016

    • Author(s)
      橋本みさき, 橋本崇史, 大塚悠伽, 高見章帆, 大矢 進, 藤井正徳
    • Organizer
      第65回日本アレルギー学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] 自動掻痒解析装置を用いたアトピー性皮膚炎モデルマウスの掻痒様行動の解析2016

    • Author(s)
      大塚悠伽, 高見章帆, 橋本みさき, 大矢 進, 藤井正徳
    • Organizer
      第129回日本薬理学会近畿部会
    • Place of Presentation
      広島
    • Related Report
      2016 Research-status Report
  • [Presentation] アトピー性皮膚炎モデルマウスのバルビツール酸系薬誘発掻痒様行動の増加におけるGABAA受容体とAMPA受容体の関与2016

    • Author(s)
      梅原祐奈, 竹内雅史, 大神彩佳, 浅野絵里香, 大矢 進, 藤井正徳
    • Organizer
      第129回日本薬理学会近畿部会
    • Place of Presentation
      広島
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都薬科大学 病態薬科学系 薬理学分野 ホームページ

    • URL

      http://labo.kyoto-phu.ac.jp/yakuri/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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