Role of interlukin-6 through CRF2 on gastric hyperalgesia in rat model of functional dyspepsia
| Project/Area Number |
17K09031
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
奥田 洋明 金沢大学, 医学系, 准教授 (40453162)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | IL-6 / 内臓痛 / 胃痛 / CRF / ストレス / 免疫組織化学 / 機能性胃腸症 / 痛覚過敏 / サイトカイン / 中和抗体 / 副腎皮質刺激ホルモン放出因子 / CRFR2 / IL-1β |
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| Outline of Final Research Achievements |
Functional dyspepsia (FD) is a common gastrointestinal disorder associated with persistent or recurrent upper gastrointestinal tract symptoms such as pain without any obvious pathological changes.
Repeated water avoidance stress (WA-S) produced gastric hyperalgesia, with no obvious lesions in the gastric mucosa. Gastric hyperalgesia was inhibited by CRF and CRF2 antagonists, suggesting their involvement in gastric hyperalgesia observed after application of stress. Gastric hyperalgesia was inhibited by IL-6 neutralizing antibody. Immunofluorescence staining demonstrated CRF, CRF2, urocortin (Ucn)1, and Ucn2-positive cells in the gastric mucosa. CRF2-positive cells increased after WA-S, compared to sham stress. CRF2 and Ucn2 were expressed in the mast cells in the gastric mucosa.
CRF2 plays an important role in gastric hyperalgesia produced by stress. CRF2 signaling may be a useful therapeutic target for functional dyspepsia.
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| Academic Significance and Societal Importance of the Research Achievements |
機能性胃腸症は頻度が高く、社会的、医療経済への影響が大きい。ストレスによって病変が見られないにもかかわらず胃の痛覚が亢進する動物モデルを確立したことは、機能性胃腸症の研究を促進することが期待される。これまで過敏性腸症候群での結腸の痛覚亢進にはCRF1の関与が示唆されてきたが、胃ではCRF2が関与しており、過敏性腸症候群とは異なるメカニズムと治療法の検討が必要となってきた。また、CRF受容体が痛覚を亢進するメカニズムはこれまで不明であったが、本研究ではじめて、IL-6の関与を明らかにした。今後CRF関連の分子に加え、IL-6が機能性消化管障害の治療の標的として有用であることを示すことができた。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice.2019
Author(s)
Yamamoto Y, Liang M, Munesue S, Deguchi K, Harashima A, Furuhara K, Yuhi T, Zhong J, Akther S, Goto H, Eguchi Y, Kitao Y, Hori O, Shiraishi Y, Ozaki N, Shimizu Y, Kamide T, Yoshikawa A, Hayashi Y, Nakada M, Lopatina O, Gerasimenko M, Komleva Y, Malinovskaya N, Salmina AB, Asano M, Nishimori K, Higashida H et al.,
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Journal Title
Commun Biol
Volume: ２
Issue: 1
Pages: 76-76
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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