2017 Fiscal Year Final Research Report
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 (海琳) 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
|
Keywords | クローン病 / 線維化狭窄 / 筋線維芽細胞 / TRPA1チャネル |
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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Free Research Field |
生理学
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