| Project/Area Number |
19K17461
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 感染後過敏性腸症候群 / Toll-like receptor 9 / Citrobacter rodentium / 過敏性腸症候群 |
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| Outline of Research at the Start |
重篤な腸炎後に生じる過敏性腸症候群（PI-IBS）において、その発生機序や詳細な病態は不明であり、治療法も確立したものがない。本研究では、ヒトPI-IBS患者の大規模追跡調査で病態発症との関連が示唆されたToll-like receptor 9(TLR9)に着目し、「TLR9シグナル異常がPI-IBSの病態にどう影響を与えるか、その機序はなにか、さらにTLR9 pathwayをターゲットとした治療が可能か」をマウスモデルとヒト検体を用いて検証する。
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| Outline of Final Research Achievements |
Wild type (WT) and Toll-like receptor 9 Knock out (KO) mice were introduced acute gastroenteritis using Citrobacter rodentium. Barostat procedure, which is the standard IBS evaluation method, were performed 6 weeks after infection. Interestingly, only TLR9KO mice developed visceral hypersensitivity. We have further investigated the mechanisms, and we found it the upregulated bradykinin B2 receptor (BDKRB2) was involved in visceral hypersensitivity.
Therefore, we are going to elucidate if the BDKRB2 can be a new therapeutic target for developing PI-IBS.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から、Toll-like recepter9欠損状態に感染性腸炎を生じることが過敏性腸症候群の発症の一因であること、腸管知覚過敏の原因としてブラジキニンB2受容体の関与が示唆された。そのため今後ブラジキニンB2受容体をターゲットとした新規の治療法の開発が期待できると考える。
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