MicroRNA overexpression to establish a new arrhythmia model for studying its molecular mechanism(Fostering Joint International Research)

2018 Fiscal Year Final Research Report

• Project/Area Number: 15KK0313
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: The University of Tokushima (2016-2018); Oita University (2015)
• Principal Investigator: MORISHIMA Masaki 徳島大学, 病院, 特任講師 (40437934)
• Research Collaborator: Singh Harpreet Drexel University, College of Medicine, Department of Pharmacology and Physiology, Associate professor
• Project Period (FY): 2016 – 2018
• Keywords: microRNA / 心房細動 / イオンチャネル / ミトコンドリア / 遺伝子改変ラット

Outline of Final Research Achievements

Our previous study has shown that microRNA-30d(miR-30d) is up-regulated in cardiomyocytes with persistent atrial fibrillation (AF), in response to cellular Ca2+-overload. However, mechanisms for miR-30d up-regulation in AF cardiomyocytes have not been elucidated. In this study, we investigated the mechanism how microRNA-30d (miR-30d) involved in the development of AF pathogenesis, we established a novel cardio-specific miR-30d overexpressed rat. MiR-30d overexpressed rats showed more vulnerable and short life span compared with wild type rats. The correlation of miR-30d expression between plasma and atrium was positively indicated in those rats. These data proposed circulating miRNA-30d as promise biomarkers and therapeutic targets in AF.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

これまでに、持続性AFの病態を的確に現わすモデル動物が存在しなかったため、新規の不整脈治療薬開発のための基盤研究の妨げとなってきたが、我々が樹立した心筋特異的miR-30d過剰発現ラットを用いて生理学的解析を行うことで、AFの病因に関わる新たな因子の同定につながることが期待される。さらに、本研究で着目したmiR-30dがAFの病態を良好に反映するバイオマーカーとして、今後臨床応用できる可能性がある。