Elucidation of the mechanisms of alloknesis (itch hypersensitivity) and development of treatment
Project/Area Number |
18K07396
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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Research Institution | Juntendo University |
Principal Investigator |
Tominaga Mitsutoshi 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (50468592)
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Co-Investigator(Kenkyū-buntansha) |
高森 建二 順天堂大学, 医学部, 特任教授 (40053144)
鎌田 弥生 順天堂大学, 医学(系)研究科(研究院), 助教 (00410035)
本田 耕太郎 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (70803625)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | アロネーシス / 脊髄 / コレシストキニン / かゆみ過敏 / 機械刺激 / 遺伝子改変 / von Frey フィラメント / CCK2受容体 / CCK8S / ドライスキン / ノックアウト / GRPR / 痒覚過敏 / アトピー性皮膚炎 / 後根神経節 |
Outline of Final Research Achievements |
This study was conducted to reveal mechanisms of alloknesis (itch hypersensitivity) involved in the pathogenesis of the itch-scratch cycle, which is a problem in atopic dermatitis, and to develop treatment. Behavioral pharmacological and histological analyses showed that the spinal cholecystokinin 8S (CCK8S)/CCK2 receptor (CCK2R) system was strongly involved in the development of alloknesis, and oral administration of CCK2R antagonists suppresses CCK8S-induced alloknesis and dry skin-induced alloknesis. These findings suggest that spinal CCK2R is a promising therapeutic target for alloknesis.
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Academic Significance and Societal Importance of the Research Achievements |
これまでアロネーシスの発症に関与する細胞種は同定されていたが、特定の分子は未同定であった。しかし、本研究では世界で初めてアロネーシス発症に特異的な分子CCK8S/CCK2Rを同定した。本研究成果は、CCK8S/CCK2Rを起点としたアロネーシス発生経路(アロネーシス・パスウェイ)の全容解明と、アロネーシスを伴う皮膚疾患の治療法の開発を加速させ、世界中の痒覚過敏で苦渋する患者のQOL向上に繋がることが期待される。
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Report
(4 results)
Research Products
(84 results)
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[Journal Article] Calcium-inducible MAPK/AP-1 signaling drives semaphorin 3A expression in normal human epidermal keratinocytes.2020
Author(s)
Kamata Y, Tominaga M, Umehara Y, Honda K, Kamo A, Moniaga CS, Komiya E, Toyama S, Suga Y, Ogawa H, Takamori K
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Journal Title
J Invest Dermatol.
Volume: ー
Issue: 7
Pages: 1346-1354
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Biological effects of IL-26 on T cell-mediated skin inflammation, including psoriasis.2019
Author(s)
Itoh T, Hatano R, Komiya E, Otsuka H, Narita Y, Aune TM, Dang NH, Matsuoka S, Naito H, Tominaga M, Takamori K, Morimoto C, Ohnuma K.
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Journal Title
J Invest Dermatol
Volume: 139
Issue: 4
Pages: 878-889
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Endomorphin preferentially induces mechanical alloknesis under the control of DPPIV enzyme.2020
Author(s)
Komiya E, Hatano R, Itoh T, Honda K, Kamata Y, Toyama S, Moniaga CS, Otsuka H, Takahashi N, Ohnuma K, Tominaga M, Morimoto C, Takamori K.
Organizer
第45回日本研究皮膚科学会
Related Report
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[Presentation] A role of spinal cholecystokinin-8/cholecystokinin 2 receptor system in itch.2019
Author(s)
Tominaga M, Honda K, Kusube F, Komiya E, Kosaka R, Takahashi N, Naito H, Yamakura F, Suga Y, Tomooka Y, Takamori K
Organizer
24th World Congress of Dermatology
Related Report
Int'l Joint Research
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[Presentation] The spinal cholecystokinin system functions in alloknesis induction2019
Author(s)
Tominaga M, Honda K, Kusube F, Komiya E, Kosaka R, Takahashi N, Naito H, Yamakura F, Suga Y, Tomooka Y, Takamori K
Organizer
28th Congress of the European Academy of Dermatology and Venereology (EADV)
Related Report
Int'l Joint Research
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[Presentation] Possible regulation of mechanical itch by CD26/DPPIV2019
Author(s)
Komiya Y, Hatano R, Itoh T, Otsuka H, Kamata Y, Honda K, Toyama S, Moniaga CS, Ohnuma K, Tominaga M, Morimoto C, Takamori K
Organizer
10th World Congress on Itch (WCI)
Related Report
Int'l Joint Research
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