Elucidation of the pathological mechanism of inflammatory bowel disease caused by vascular endothelial damage

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08692
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Juntendo University
• Principal Investigator: Osada Taro 順天堂大学, 医学部, 教授 (00338336)
• Co-Investigator(Kenkyū-buntansha): 服部 浩一 順天堂大学, 大学院医学研究科, 特任先任准教授 (10360116)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 小腸大腸肛門外科学 / 下部消化管学 / 炎症性腸疾患 / 潰瘍性大腸炎 / 生体分子

Outline of Final Research Achievements

Inflammatory bowel disease(IBD) has attracted attention for the efficacy of biologics against TNFα. We have investigated whether TNFα secretion in disease model organisms of cytokine storm syndrome(CSS), such as graft-versus-host disease(GVHD) and malignant melanoma-induced cancer chahexia, is mediated by angiocrine factor dynamics through matrix metalloproteinases. by an increase in plasminogen activator inhibitor(PAI-1), and a decrease in free urokinase-type PA(uPA), as well as the efficacy of a new siRNA-based nucleic acid preparation for the angiocrine factor CD40. In addition, as a clinical study, the importance of fibrinolytic system activity kinetics such as PAI-1 and uPA as biomarkers in the end-blood of CSS severity, such as TNFα, interferon-γ and IL-6 based on COVID-19, has been reported, and the biomarker of IBD disease status and novel molecular therapy of angiocline factor confirming its usefulness as a target for novel molecular therapies(submission in preparation).

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

IBDに対する治療法は特定のサイトカインやシグナル伝達をブロックする分子標的薬および血球成分除去療法の普及により、その長期予後は有意に改善されつつあるが、未だ厳然と内科治療の不応例および長期罹患例には癌化症例が存在することが判明しており、発症早期での病勢制御がこれからは必要不可欠になってくる。本研究成果はIBDの長期的な予後、QOLの改善、またその病勢制御に必須な知見を提示した。また、IBDのみならずCOVID-19をはじめとするサイトカインストームを呈する病態の治療効果戦略への糸口として重要な結果を示唆したものと言える。