Development of novel therapeutics targeting mitochondria DNA

Research Project

Project/Area Number	15K19387
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Cardiovascular medicine
Research Institution	Kyushu University
Principal Investigator	fujino takeo 九州大学, 医学研究院, 助教 (10721904)
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	ミトコンドリア / 心不全 / 心筋リモデリング / 酸化ストレス / ミトコンドリアDNA / リモデリング
Outline of Final Research Achievements	The purpose of this study was to investigate the mechanism of anti-remodeling effect by mtDNA. We generated volume overload model mice in Twinkle helicase overexpression mice (TW mice) and Tfam overexpression mice (TF mice). TW mice and TF mice increased mtDNA copy number by different mechanism respectively, furthermore each mice suppressed left ventricular remodeling and repressed mitochondrial oxidative stress. However, because oxidative stress were induced in mtDNA, that mtDNA can function as ROS regulatory factor in mitochondria. Furthermore, it was also identified that pressure overload model mice in TW mice and TF mice led to reduction in fibrogenesis and suppression of MMP generation.