Elucidation of the entropy of tissue damage in digestive organs and development of new therapeutic approaches

2023 Fiscal Year Final Research Report

• Project Area: Integrated elucidation of inflammatory tissue-resilience and tissue damage-entropy;Creation of innovative science for resolution of inflammation
• Project/Area Number: 21H05123
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Keio University
• Principal Investigator: MIKAMI YOHEI 慶應義塾大学, 医学部(信濃町), 准教授 (80528662)
• Project Period (FY): 2021-08-23 – 2024-03-31
• Keywords: 炎症収束 / 炎症性腸疾患 / 肝炎 / 潰瘍性大腸炎 / クローン病

Outline of Final Research Achievements

In this study, we successfully established an intestinal fibrosis model induced by intestinal epithelial detachment to address the lack of model animals in the research of intestinal tissue remodeling or increase in entropy. Using the newly established intestinal fibrosis model animals and human samples, we conducted unbiased analyses of bulk RNA-seq and scRNA-seq data of stromal cells in the intestine, revealing the functional diversity of intestinal resident stromal cells. Furthermore, through integrative multi-omics analysis incorporating transcriptomic and epigenomic analyses such as ATAC-seq, we identified a novel fibroblast population that specifically arises during intestinal fibrosis.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患を含む広義の自己免疫性疾患の治療法として、分子標的療法は炎症制御に関しては革新的な治療革命をもたらしたものの、炎症収束後の組織レジリエンスには効果が乏しく、未だ炎症性腸疾患の根治療法は得られていない。本研究では、Omics解析を用いて、腸管組織障害に関与する新規のストローマ細胞集団を同定し、その分化経路の一端を明らかとするとともに、新規のストローマ細胞を標的とした革新的抗線維化治療に繋がる基盤的検討を示すことに成功した。ヒト検体およびモデル動物間の相同性相違性を解析することにより、種差を超えた普遍的な腸管組織エントロピー増大機構の一端を明らかとした。