Analysis of mechanisms for the refractoriness of small intestinal lesions in inflammatory bowel diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takenaka Kento 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座講師 (10783368)
• Co-Investigator(Kenkyū-buntansha): 土屋 輝一郎 筑波大学, 医学医療系, 教授 (40376786) ; 岡本 隆一 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: クローン病 / オルガノイド / 小腸病変

Outline of Final Research Achievements

The applicant first discovered the refractoriness of small intestinal lesions in inflammatory bowel diseases. In this study, we used in vitro models of inflammation and clinical samples from Crohn's disease patients to identify key molecules that regulate the refractoriness of small intestinal lesions in inflammatory bowel diseases.
Long-term cultures in human small intestinal organoids were attempted, but it was not possible to maintain the cultures for more than 30 weeks. This suggests that small intestinal epithelial cells may be less resistant to inflammatory responses than colonic epithelial cells. On the other hand, the quantification of inflammatory cytokines, oxidative stress factors and telomere length showed no significant differences compared to colonic epithelial cells. On the other hand, a comprehensive microarray analysis identified several candidate factors, and further analysis is planned to narrow down the candidate factors that define intestinal lesion susceptibility.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

臓器特異的な炎症脆弱機構の発見は独創的であり、申請者らにのみ遂行可能な研究と考える。また小腸特異的炎症脆弱性機構の発見は、クローン病以外の他の小腸炎症性難病にも応用されることが期待でき、新規治療薬の開発など発展性・創造性に富む研究である。