• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

Analysis for Molecular Mechanism of Cardiomyocyte Differentiation by Using a Cell Line Which Efficiently Differentiates into Cardiomyocytes

Research Project

Project/Area Number 12835003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionThe University of Tokyo

Principal Investigator

HAYASHI Doubun  The University of Tokyo, The University of Tokyo, Graduate School of Medicine, visiting associate professor (80313104)

Co-Investigator(Kenkyū-buntansha) KOMURO Issei  The University of Chiba, Graduate School of Medicine Department of Cardiovascular Medicine, Professor (30260483)
HIROI Yukio  University Hospital, 医学部附属病院, Research Associate (30311624)
Project Period (FY) 2000 – 2002
KeywordsRegeneration Medicine / BMP / Smad / TAK1 / ATF-2 / Transcription Factor / Cardiomyocyte Differentiation / P19CL6
Research Abstract

The aims of basic research for understanding the molecular mechanism of cardiomyocyte differentiation and cardiac development include the establishment of the genetic technique by which cardiomyocyte differentiation can be induced, which may contribute to the practical therapeutic application for tissue regeneration and the subsequent gene-therapy for heart failure. From this respect, we investigated the molecular mechanism by which cardiomyocyte differentiation is regulated by using a cardiomyogenic cell line, P19CL6, which can differentiate efficiently into beating cardiomyocytes.
We previously demonstrated that bone morphogenetic proteins (BMPs) induce cardiornyocyte differentiation through the MAPKKK TAK1. Transcription factors Smads have been reported to play a critical role in BMP signaling and the ATF/CREB family transcription factor ATF-2 has recently been shown to be a common nuclear target of the Smad and the TAK1 pathways. We here examined whether Smads and ATF-2 are involved … More in cardiomyocyte differentiation using P19CL6, a clonal derivative of murine P19 cells. Although P19CL6 efficiently differentiates into cardiomyocytes when treated with dimethyl sulfbxide, P19CL6noggin, a P19CL6 cell line constitutively overexpressing the BMP antagonist noggin, did not differentiate into cardiomyocytes. Co-overexpression of Smadl, a ligand-specific Smad, and Smad4, a common mediator Smad, restored the ability of P19CL6noggin to differentiate into cardiomyocytes, whereas stable overexpression of Smad6, an inhibitory Smad, completely blocked differentiation of P19CL6, suggesting that the Smad pathway is necessary for cardiomyocyte differentiation. ATF-2 stimulated βMHC promoter acitvity by the synergistic manner with Smad1/4 and TAK1, while overexpression of the dominant negative form of ATF-2 reduced the promoter activities of several cardiac-specific genes and inhibited cardiomyocyte differentiation of P19CL6. These results suggest that Smads, TAK1, and their common target ATF-2 cooperatively play a critical role in cardiomyocyte differentiation. Less

  • Research Products

    (12 results)

All 2002 2001 2000

All Journal Article (12 results)

  • [Journal Article] A role for bone morphogenetic protein signaling in cardiomyocyte differentiation.2002

    • Author(s)
      Monzen K., et. al.
    • Journal Title

      Trends Cardiovasc Med. 12

      Pages: 263-269

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A role for bone morphogenetic protein signaling in cardiomyocyte differentiation.2002

    • Author(s)
      Monzen K, et. al.
    • Journal Title

      Trends Cardivasc Med 12

      Pages: 263-269

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation.2001

    • Author(s)
      Hiroi Y., et. al.
    • Journal Title

      Nat Genet 28(3)

      Pages: 276-280

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A nove myocyte-specific gene Midori promotes the differentiation of P19CL6 cells into cardiomyocytes.2001

    • Author(s)
      Hosoda T., et. al.
    • Journal Title

      J Biol Chem. 276(38)

      Pages: 35978-35989

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Smads, TAKI, and their common target ATF-2 play a crinical role in cardiomyocyte differentiation.2001

    • Author(s)
      Monzen K., et. al.
    • Journal Title

      J Cell Biol. 153(4)

      Pages: 687-698

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte defferentiation.2001

    • Author(s)
      Hiroi Y., et. al.
    • Journal Title

      Nat Genet 28(3)

      Pages: 276-280

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel myocyte-specific gene Midori promotes the differentiation of P19CL6 cells into cardiomyocytes.2001

    • Author(s)
      Hosoda T., et. al.
    • Journal Title

      J Biol Chem 276(38)

      Pages: 35978-35989

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Smads, TAK1, and their common target ATF-2 play a crinical role in cardiomyocyte differentiation.2001

    • Author(s)
      Monzen K, et. al.
    • Journal Title

      J Cell Biol 153(4)

      Pages: 687-698

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Up-reguation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice.2000

    • Author(s)
      Takimoto E., et. al.
    • Journal Title

      Biochemical & Biophysical Research Communications 270(3)

      Pages: 1074-1079

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ca2+calmodulin-dependent kinase II and calcineurin play critical roles in endnthelin-1-induced cardiomyocyte hypertrophy.2000

    • Author(s)
      Zhu W., et. al.
    • Journal Title

      Journal of Biological Chemistry 275(20)

      Pages: 15239-15245

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice.2000

    • Author(s)
      Takimoto E., et. al.
    • Journal Title

      Biochemical & Biophysical Research Communications 270(3)

      Pages: 1074-1079

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ca2+calmodulin-dependent kinase II and calcineurin play critical roles in endothelin-1-induced cardiomyocyte hypertrophy.2000

    • Author(s)
      Zhu W., et. al.
    • Journal Title

      Journal of Biological Chemistry 275(20)

      Pages: 15239-15245

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2011-06-18  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi