Elucidation of the physiological significance of PTK6 family kinases and their application to pathological analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07117
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Microbial Chemistry Research Foundation (2022-2023); The University of Tokyo (2021)
• Principal Investigator: Kikuchi Ippei 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (80772376)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: チロシンキナーゼ / がん / 粘膜免疫 / ゲノム編集 / 回腸

Outline of Final Research Achievements

In this study, we generated PFK triple-knockout mice by simultaneously disrupting three PTK6 family kinases (PFKs) using genome editing. As a result, the PFK triple-knockout mice exhibited abnormalities in intestinal epithelial homeostasis in the ileum, the terminal part of the small intestine. Additionally, these mice showed activation of mucosal immune responses and dysbiosis of the gut microbiota in the ileum. Furthermore, phylogenetic analysis revealed that PFKs and the gastrointestinal tract may have co-evolved, suggesting that the robustness of ileal functions, which are crucial for nutrient absorption and mucosal immunity in higher vertebrates, was acquired through this co-evolution.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまで生理的機能が全く不明であったPTK6ファミリーキナーゼの生体内機能と病態との関連を調べた。その結果、PTK6ファミリーキナーゼは小腸の末端部位である回腸における組織恒常性や粘膜免疫の調節に必須の役割を担うことを明らかにした。本研究の成果は、回腸が好発部位である炎症性腸疾患「クローン病」や自己免疫疾患などの疾患に対する新たな治療法開発に役立つことが期待される。