Elucidating the mechanism of abnormal protein aggregation in sporadic inclusion body myositis by single molecule nanoimaging

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19505
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Tohoku University
• Principal Investigator: Aoki Masashi 東北大学, 医学系研究科, 教授 (70302148)
• Co-Investigator(Kenkyū-buntansha): 割田 仁 東北大学, 大学病院, 助教 (30400245) ; 鈴木 直輝 東北大学, 医学系研究科, 非常勤講師 (70451599)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 封入体筋炎 / RNAシークエンス / 電気収縮培養 / TDP-43 / プロテアソーム / 骨格筋生物学

Outline of Final Research Achievements

In this study, myoblasts were harvested from sporadic inclusion body myositis (sIBM) patients during muscle biopsy, and a total of six lines were stocked during these two years. Cellular stress was applied to human skeletal muscle using electro-pulse-constriction-culture-system (EPS) which reproduces long-lasting muscle contraction. Analysis was performed by RNA sequencing using cells before and after contraction stress. The characteristics of the co-culture system (EPS culture) were reported in an international journal. In addition, TDP-43, which is a component of the aggregates, is labeled by single-molecule nanoimaging, and the presence or absence of aggregate formation before and after EPS culture was evaluated. Furthermore, analysis of the myoblast specific proteasome deficient mouse revealed that p53 is important for the maintenance of myoblasts pool.

Free Research Field

臨床神経学

Academic Significance and Societal Importance of the Research Achievements

学術的には2報の論文を国際誌に掲載することができた。一つは封入体筋炎の病態に関与すると考えられる蛋白分解系であるプロテアソームの骨格筋における役割をStem Cell Reports誌に、もう一つは本研究課題の主要評価系である電気収縮培養のシステムとしての有用性についてSciRep誌に、それぞれ報告した。今後、本研究を発展させるうえで、いずれも重要な論文である。前者はプレスリリースも行い、社会的にも骨格筋生物学研究の意義について広く周知することができた。