The investigation of the role of early-postnatal expressing genes in cardiomyocyte proliferation

• Project/Area Number: 16K09497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: NAKASHIMA YASUHIRO 京都大学, 医学研究科, 特定病院助教 (20565585)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心筋分化 / 細胞増殖 / 心発生

Outline of Final Research Achievements

In this study, we investigated the molecular function of the genes that are expressed in the heart specifically before early-postnatal stage and also promote cell proliferation. Part of the genes were expressed specifically from non-cardiomyocytes. It was shown that CRP1 was expressed specifically in fetal and neonatal cardiomyocytes and also promoted the proliferation of cardiac myoblast cell line, and that CRP1 and MLP, its farmily gene expressed in cardiomyocytes over adulthood had a distinct effect on proliferation and gene expression, suggesting that the difference of expression level of these LIM proteins, at least in part, would potentially lead to a distinct cell function between fetal and adult cardiomyocytes .

Academic Significance and Societal Importance of the Research Achievements

CRP1およびMLPは心血管疾患に関わる遺伝子であるが、その分子機能については未だ不明な点が多い。本研究ではその分子機能やヒト変異における分子機能異常について新たな知見を見出した。これらの機能解明は心血管疾患の成因、病態および遺伝的要因の意義についての理解をさらに進める上で重要であり、より優れた治療・予防法・リスク評価の構築につながるものである。

Research Products

• [Journal Article] Dynamic changes of serum microRNA-122-5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation. (2017)
  • Author(s): Satoshi Koyama, Takashi Kuragaichi, Yukihito Sato, Yasuhide Kuwabara, Shunsuke Usami, Takahiro Horie, Osamu Baba, Daihiko Hakuno, Yasuhiro Nakashima, Tomohiro Nishino, Masataka Nishiga, Tetsushi Nakao, Hidenori Arai, Takeshi Kimura, Koh Ono
  • Journal Title: ESC Heart Failure Volume: 4 Issue: 2 Pages: 112-121
  • DOI: 10.1002/ehf2.12123
  • Peer Reviewed / Open Access
• [Journal Article] Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model. (2017)
  • Author(s): Izuhara M, Kuwabara Y, Saito N, Yamamoto E, Hakuno D, Nakashima Y, Horie T, Baba O, Nishiga M, Nakao T, Nishino T, Nakazeki F, Ide Y, Kimura M, Kimura T, Ono K.
  • Journal Title: PLoS One Volume: 12(3) Issue: 3 Pages: e0172798-e0172798
  • DOI: 10.1371/journal.pone.0172798
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol. (2016)
  • Author(s): Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K.
  • Journal Title: Circ Res. Volume: - Issue: 5 Pages: 835-847
  • DOI: 10.1161/circresaha.116.309528
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant