Molecular mechanism of tight junction maintenance by proteases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Higashi Tomohito 福島県立医科大学, 医学部, 准教授 (70515072)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 密着結合（タイトジャンクション）

Outline of Final Research Achievements

Epithelial tight junctions (TJs) regulate the paracellular permeability of substances and maintain barrier function. Although TJs are challenged by cell movements and tension changes and undergo small breaks, the mechanisms that repair and maintain TJs have not been clarified. In this study, I discovered that a transmembrane protein EpCAM is complexed with claudin-7, a building block of TJs, and that EpCAM-claudin 7 complex is maintained on the basolateral membranes. Upon TJ break, membrane-anchored serine proteinase family proteinases cleave EpCAM and release the complexed claudin-7, which participates in the repair process of TJ breaks. This study uncovered a novel mechanism of epithelial barrier maintenance.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞間接着装置の一つである密着結合は、体の中の異なる区画の間の液性成分の移動を制限・制御することによって上皮組織が正常な生理機能を果たせるようにしています。本研究は密着結合が、生じてしまった小さなキズを常に修復しているという新しい概念に基づき密着結合の維持機構の一端を解明しました。本研究成果は、密着結合関連疾患の病態解明につながるとともに、この維持機構を一過的に阻害することにより、鼻腔や消化管などの密着結合を一時的にゆるめて効率的に薬剤を送達する手法の開発などにつながる可能性があります。