In vivo screening for gastrointestinal stricture therapy targeting TRPA1 channel
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 |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Fukuoka University |
Principal Investigator |
Kurahara Lin 福岡大学, 医学部, 講師 (00341438)
|
Research Collaborator |
HIRAISHI Keizo
HU Yaopeng
KOGA Kaori
ONITSUKA Miki
DOI Mayumi
AOYAGI Kunihiko
TAKEDATSU Hidetoshi
KOJIMA Daibo
FUJIHARA Yoshitaka
JIAN Yuwen
INOUE Ryuji
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
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)
|
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 |
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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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Modulation of cardiac connexin-43 by omega-3 fatty acid ethyl-ester supplementation demonstrated in spontaneously diabetic rats.2015
Author(s)
Radosinska J, Kurahara LH, Hiraishi K, Viczenczova C, Egan Benova T, Szeiffova Bacova B, Dosenko V, Navarova J, Obsitnik B, Imanaga I, Soukup T, Tribulova N.
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Journal Title
Physiological Research
Volume: 64
Pages: 795-806
Related Report
Peer Reviewed / Int'l Joint Research
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