Dynamics of cardiac stem cells in myocardial repair/regeneration and regulation of their cell fate by cytokines

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390069
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: FUJIO Yasushi Osaka University, 大学院・薬学研究科, 教授 (20359839)
• Co-Investigator(Kenkyū-buntansha): AZUMA Junichi 大阪大学, 大学院・薬学研究科, 教授 (30144463) ; MAEDA Makiko 兵庫医療大学, 薬学部, 講師 (70461168)
• Project Period (FY): 2008 – 2010
• Keywords: 組織幹細胞 / サイトカイン / 心筋リモデリング / 細胞運命 / 心臓

Research Abstract

So far, cardiac regenerative activity has been believed to be trivial; however, recent studies have demonstrated that pluripotent stem cells exist in myocardium. In this study, we addressed the molecular mechanisms of cardiac stem cell differentiation and examined the cellular dynamics of the cardiac stem cell-derived endothelial cells in infarct myocardium. And we found that IL-6 family cytokines induce endothelial differentiation from cardiac stem cells through STAT3/Pim-1 pathway both in vitro and in vivo.

Research Products

• [Journal Article] STAT3/Pim-1 signaling pathway plays a crucial role in endothelial differentiation of cardiac resident stem cells both in vitro and in vivo. (2011)
  • Author(s): Iwakura T., Mohri T., Hamatani T., Obana M., Yamashita T., Maeda M., Katakami N., Kaneto H., Komuro I., Azuma J., Nakayama H., Fujio Y.
  • Journal Title: J.Mol.Cell.Cardiol. In press
• [Journal Article] SHP2 negatively regulates skeletal alpha-actin gene expression downstream of gp130 signaling in cardiomyocytes. (2010)
  • Author(s): Nakaoka Y., Shioyama W., Kunimoto S., Fujio Y., Higuchi K., Nishida K., Arita, Y., Kuroda T., Hirota H., Yamauchi-Takihara K., Hirano T., Komuro I., Mochizuki N.
  • Journal Title: J.Mol.Cell.Cardiol. 49 Pages: 157-164
• [Journal Article] Therapeutic activation of STAT3 by interleukin-11 ameliorates cardiac fibrosis after myocardial infarction. (2010)
  • Author(s): Obana M., Maeda M., Takeda K., Hayama A., Mohri T., Yamashita T., Nakaoka Y., Komuro I., Takeda K., Matsumiya G., Azuma J., Fujio Y.
  • Journal Title: Circulation. 121 Pages: 684-691
• [Journal Article] IL-11の心血管系における作用 (2010)
  • Author(s): 尾花理徳、前田真貴子、藤尾慈
  • Journal Title: 循環器科 67 Pages: 156-162
• [Journal Article] Signals through glycoprotein 130 regulate the endothelial differentiation of cardiac stem cells. Arterioscler. (2009)
  • Author(s): Mohri T., Fujio Y., Iwakura T., Matsuda K., Maeda M., Azuma J.
  • Journal Title: Thromb.Vasc.Biol. 29 Pages: 754-760
• [Journal Article] Atrogin-1 ubiquitin ligase is upregulated by doxorubicin via p38 MAP kinase in cardiac myocytes. (2008)
  • Author(s): Yamamoto, Y., Hoshino, Y., Ito, T., Nariai, T., Mohri, T., Obana M., Hayata, N., Uozumi, Y., Maeda M., Fujio Y., Azuma, J.
  • Journal Title: Cardiovasc.Res. 79 Pages: 89-96
• [Presentation] Drug Dosing Considerations for Antithrombotic Therapy (2009)
  • Author(s): Fujio, Y.
  • Organizer: Session : Joint AHA/Asian Pacific Society of Cardiology : Pharmacogenomics : Implications for Drug Dosing and Clinical Trials in Different Populations. American Heart Association, Scientific Session 2009
  • Place of Presentation: Orlando
  • Year and Date: 20091114-20091118
• [Presentation] Cytokine Session : How to Recognize Cell Death and Its Impact on Heart Failure American Heart Association (2008)
  • Author(s): Fujio, Y.
  • Organizer: Scientific Session 2008
  • Place of Presentation: New Orleans
  • Year and Date: 20081108-20081112