Analysis of the mechanism of maturation and differentiation of the heart cells during development

• Project/Area Number: 16K08469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Osaka University (2019); Kumamoto University (2016-2018)
• Principal Investigator: Koibuchi Nobutaka 大阪大学, 医学系研究科, 招へい准教授 (30456131)
• Co-Investigator(Kenkyū-buntansha): 山口 雅裕 鈴鹿工業高等専門学校, その他部局等, 准教授 (00360660)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 心臓 / 心室 / 転写因子 / 心室筋 / 細胞分化 / 発生 / 分化 / 発生・分化

Outline of Final Research Achievements

The Hey2 (hairy and enhancer of split-related with YRPW motif 2) is reported to play potential roles in ventricular maturation during heart development. However, the underlying mechanism is remained unknown. To identify potential mechanisms by which Hey2 affects myocardial development, we performed a systematic analysis of regional myocardial gene expression. We identified the transcriptional factor that is associated with Hey2.

Academic Significance and Societal Importance of the Research Achievements

近年の研究により、Hey2遺伝子の変異はブルガタ症候群（元気だった成人が、突然心臓が停止してしまい死にいたる病気で、古くは「ぽっくり病」と呼ばれていた）の発症に強い関連性があることが明らかとされた。それらの研究から、ブルガタ症候群は成人で発症することが多いのだが、実は先天性心疾患の一つであって、すでに胎生期の心臓でHey2に関連した転写因子による遺伝子発現調節機構の異常が起こっており、それが発症原因であるとも指摘されている。本研究の成果により原因不明なブルガタ症候群の発症機序の解明に繋がることが期待される

Research Products

• [Journal Article] Local Production of Activated Factor X in Atherosclerotic Plaque Induced Vascular Smooth Muscle Cell Senescence. (2017)
  • Author(s): Sanada F, Muratsu J, Otsu R, Shimizu H, Koibuchi N, Uchida K, Taniyama Y, Yoshimura S, Rakugi H, Morishita R.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 17172-17172
  • DOI: 10.1038/s41598-017-17508-6
  • Peer Reviewed / Open Access
• [Journal Article] Detrimental Effects of Centrally Administered Angiotensin II are Enhanced in a Mouse Model of Alzheimer Disease Independently of Blood Pressure. (2017)
  • Author(s): Takane K, Hasegawa Y, Lin B, Koibuchi N, Cao C, Yokoo T, Kim-Mitsuyama S.
  • Journal Title: J Am Heart Assoc. Volume: 6 Issue: 4
  • DOI: 10.1161/jaha.116.004897
  • Peer Reviewed / Open Access
• [Journal Article] Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome. (2017)
  • Author(s): Kusaka H, Koibuchi N, Hasegawa Y, Ogawa H, Kim-Mitsuyama S.
  • Journal Title: Cardiovasc Diabetol. Volume: 15 Pages: 157-157
  • Peer Reviewed / Open Access
• [Journal Article] High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders. (2016)
  • Author(s): Lin B, Hasegawa Y, Takane K, Koibuchi N, Cao C, Kim-Mitsuyama S.
  • Journal Title: J Am Heart Assoc. Volume: 5 Issue: 6
  • DOI: 10.1161/jaha.115.003154
  • Peer Reviewed / Open Access