Creation of New Therapeutic Strategy for Inflammatory Bowel Disease Aiming to Prevent Relapse Based on Rebuilding Mucosal Barrier

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto Pharmaceutical University (2023); University of Toyama (2021-2022)
• Principal Investigator: Hayashi Shusaku 京都薬科大学, 薬学部, 准教授 (10548217)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 動的ネットワークバイオマーカー / ゆらぎ / 未病 / Wars / ヒトIBD

Outline of Final Research Achievements

In this study, we applied DNB analysis, a new mathematical analysis method that focuses on fluctuations in gene expression and scientifically and objectively captures the transition from a healthy state to a disease state, to IBD model mice with the aim of predicting relapse and providing preventive intervention. As a result, we detected a tipping point, i.e., a pre-disease state (Me-byo), in which 27 DNB genes fluctuate substantially and synchronously before the onset of colitis. Next, to determine the pathophysiological significance of the 27 DNB genes, we calculated control theory-based DNB intervention scores and investigated the expression of the 27 DNB genes in human patients with IBD by reanalyzing datasets in the GEO database. We then intervened in Wars among the 27 DNB genes, suggesting that Wars plays a protective role in IBD.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、IBDモデルでのDNB解析さらに制御理論解析を行うことで見出されたDNB遺伝子Warsが、IBD病態において病態生理学的意義がある分子であることを初めて示したものである。また、実際にWARSを含むいくつかのDNB遺伝子の発現は、ヒトIBDの病態と関連して変動しており、病態によっては揺らぐ可能性を見出した。よってWARSをはじめとするDNB遺伝子の揺らぎを抑制させることが、再燃予防や寛解維持を通したIBD病態の改善に繋がる可能性が考えられる。