Relationship between cardiovascular and muscular disorders via GATA4

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Shinshu University
• Principal Investigator: Takaya Tomohide 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教(特定雇用) (00450883)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨格筋

Outline of Final Research Achievements

Cardiovascular disorders and muscular diseases are considered to be related because transcription factor GATA4 is commonly expressed both in cardiomyocytes and skeletal muscle stem cells. By high- throughput screening using myoblasts, we identified a novel 18 nt-oligodeoxynucleotide, named myoDN, which intensively induces myogenic differentiation. myoDN also enhanced myocardial differentiation of pluripotent stem cells. myoDN is considered to be regulate cell fates by affecting the common target(s) existing both in cardiac and skeletal muscle. myoDN improved the deteriorated myoblast differentiation of diabetic patients. It indicates that myoDN will be a useful molecule for prevention and therapy of muscle atrophy caused by cardiovascular and metabolic disorders.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

心筋や骨格筋の分化を誘導するオリゴDNAはmyoDNが世界初である。myoDNは革新的な核酸分子として、筋萎縮に代表されるロコモティブ症候群の予防・治療に有用な医薬品や機能性食品の素材として応用展開が期待される。また、myoDNを投与するだけでiPS細胞の心筋分化が著明に誘導されることから、心臓再生療法や創薬スクリーニングに不可欠な心筋細胞の作成に貢献できると考えられる。本研究成果を基盤として、myoDNと類似の作用を示す新規オリゴDNA配列や、myoDNの作用を増強する小分子を同定するなど、オリゴDNAによる細胞分化の制御技術の開発も進んでいる。