Role of exosomes as secretory vesicles in the pathophysiology of rheumatoid arthritis

Research Project

Project/Area Number	17K19405
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Research Field	Biology of Cells to Organisms, and related fields
Research Institution	Iwate Medical University
Principal Investigator	NARABA HIROAKI 岩手医科大学, 薬学部, 教授 (90296517)
Project Period (FY)	2017-06-30 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000) Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	エクソソーム / 慢性関節リウマチ / マイクロRNA / プロスタグランジン
Outline of Final Research Achievements	Exosomes are vesicles secreted by cells and have been implicated in various pathological conditions. In this project, we analyzed the microRNAs contained in blood exosomes of mice with rheumatoid arthritis. Microarray analysis of blood exosomes was performed to comprehensively analyze the expression. We examined the correlation between this information and the scored inflammatory state of arthritis, and identified several disease-linked microRNAs. It was clarified that the expression level of specific microRNA correlates well with the spread of inflammatory symptoms. These microRNAs are closely related to the onset and progression of inflammatory pathologies, and are considered to have potential for therapeutic target molecule identification and disease markers.
Academic Significance and Societal Importance of the Research Achievements	急性炎症と異なり、慢性炎症は長期のストレス応答などにより炎症反応の遷延化が生じ、機能破綻につながり、生活習慣病やがんなどの病態の基盤となっていることが提唱されている。この様な自然炎症と呼ばれる状態の病態生理に関して、現在、様々なアプローチが行われているが、まだ充分な理解には至っていない。本研究から慢性関節リウマチなどの遷延化炎症状態におけるエクソソームの関与とそこに含まれる特定分子種のmicroRNAの重要性を示すことが出来た。本研究の進展は、将来、難治性疾患等を発症する可能性を早期に見極め、その対応と発症予防につながるものと考えられる。