How EpCAM and TROP2 function in the gastrointestinal tract

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07990
• 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: Kanagawa Institute of Industrial Sclence and Technology
• Principal Investigator: Nakato Gaku 地方独立行政法人神奈川県立産業技術総合研究所, 「腸内細菌叢」プロジェクト, サブリーダー (20584535)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: TROP2 / EpCAM / 腸管上皮細胞 / 免疫細胞 / 粘膜免疫

Outline of Final Research Achievements

Epithelial cell adhesion molecules (EpCAM) and TROP2 are homologous cell surface proteins that are widely expressed, and often co-expressed, in developing and adult epithelia. EpCAM and TROP2 have various reported functions and we aim to elucidate responsible mechanisms by characterizing and investigating if they have similar or different functions. To clarify this, we studied the roles of EpCAM and TROP2 expressed in normal cells by analyzing transgenic EpCAM null mice with TROP2 expressed in the intestinal epithelial cells. Comprehensive RNA-seq analysis of the transgenic mice showed that EpCAM expressed in intestinal epithelium is involved in mucosal immunity regulation or homeostasis maintenance in both small intestine and colon, but not TROP2. We also found that EpCAM-positive CD45-positive cells are present in the gut lamina propria through mice phenotype analysis.

Free Research Field

粘膜免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では腸管上皮細胞に恒常的に発現するEpCAMが粘膜免疫の構築や維持に重要な役割を果たす可能性および、消化管粘膜固有層において、EpCAM陽性CD45陽性細胞が存在することを新たに見出した。また、腸内細菌叢解析により、腸炎を増悪させることが示唆される腸内細菌を同定した。今後、より詳細な解析を続けることで、EpCAMによる粘膜免疫系の調整もしくは制御機構が明らかにでき、新たな腸内細菌による腸炎誘導機構の解明も期待される。本成果は基礎生物学の理解を深めるのみならずEpCAMやTROP2が素因となる疾患治療法の開発への応用にも利用でき、医療の発展に貢献できる。