Extracellular function of leaked intracellular proteins: role and action in receptor-sharing monocytes and endothelial cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Yamaguchi University
• Principal Investigator: IZUMI Tomonori 山口大学, 大学院医学系研究科, 准教授 (00261694)
• Co-Investigator(Kenkyū-buntansha): 田岡 万悟 首都大学東京, 理学研究科, 准教授 (60271160)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞質漏出 / 血管内皮 / 組織修復

Outline of Final Research Achievements

Various intracellular proteins are leaked from the damaged tissue. However, significance of their extracellular function remains largely unknown. We have previously identified a novel extracellular functional molecule that exerts an action on monocytes. To clarify the role of this functional molecule in intravascular events in the acute phase, the effect on endothelial cells was analyzed. In the cell culture experiment using human vascular endothelial cells, no clear effect of functional molecules on the interaction between monocytes and endothelium or the adhesion between endothelial cells was observed. On the other hand, the motility of endothelial cells was markedly increased, and it was revealed that this functional molecule acts not only on monocytes but also on vascular endothelium. This suggests that proteins leaked from damaged tissues are directly involved in acute inflammation and tissue repair.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究により、既知の細胞内タンパク質が、細胞外では予想外の新しい役割を果たしていることが明らかとなった。急性期病態という観点からは、組織損傷により漏出した細胞内タンパク質が、血管内での炎症や組織修復などに直接作用していることを示しており、病態を左右する新たな機序のひとつになるかもしれない。漏出細胞内タンパク質の役割を新たな軸のひとつとしてとらえ、血管内イベント全体についての理解が進めば、病態のモニターや新しいタイプの創薬ターゲットとして、臨床への応用も期待できる。