| Project/Area Number |
15K08978
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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 |
Gastroenterology
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| Research Institution | Fukuoka University |
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Principal Investigator |
Kurahara Lin 福岡大学, 医学部, 講師 (00341438)
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| Research Collaborator |
HIRAISHI Keizo
HU Yaopeng
KOGA Kaori
ONITSUKA Miki
DOI Mayumi
AOYAGI Kunihiko
TAKEDATSU Hidetoshi
KOJIMA Daibo
FUJIHARA Yoshitaka
JIAN Yuwen
INOUE Ryuji
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | クローン病 / 線維化狭窄 / 筋線維芽細胞 / TRPA1チャネル / ステロイド / ピルフェニドン / myofibroblast / TRPA1 / inflammation / fibrosis / Crohn's disease / stenosis / 消化管線維化狭窄 / 線維芽細胞 / カルシウム / コラーゲン |
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| Outline of Final Research Achievements |
We investigated the anti-fibrotic effects of TRPA1 channel agonists in intestinal myofibroblasts. In stenotic intestinal regions of CD patients, TRPA1 expression was increased significantly. TRPA1/heat shock protein 47 double-positive cells accumulated in the stenotic intestinal regions of both CD patients and TNBS-treated mice. In TNBS chronic colitis model mice, the extents of inflammation and fibrotic changes were more prominent in TRPA1-/- knockout than in wild-type mice. One-week enema administration of prednisolone suppressed fibrotic lesions in wild-type mice, but not in TRPA1 knockout mice. Steroids, pirfenidone and the active ingredients of DKT, i.e., hydroxy α-sanshool and 6-shogaol activat TRPA1 channel and counteracted TGF fibrosis signaling in InMyoFibs. TRPA1, in addition to its anti-inflammatory actions, may protect against intestinal fibrosis, thus being a novel therapeutic target for highly incurable inflammatory/fibrotic disorders.
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