In vivo screening for gastrointestinal stricture therapy targeting TRPA1 channel

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08978
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• 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.

Free Research Field

生理学