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Elucidation of significance of derangement of cell differentiation in metabolic syndrome ("cell mapping) and development of cell re-differentiation therapy using human ES cells

Research Project

Project/Area Number 17390270
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKeio University (2006)
Kyoto University (2005)

Principal Investigator

ITOH Hiroshi  Keio University, School of Medicine, Professor, 医学部, 教授 (40252457)

Co-Investigator(Kenkyū-buntansha) YAMASHITA Jun  Kyoto University, Institute of Frontier Science, Professor, 再生医科学研究所, 助教授 (50335288)
EBIHARA Ken  Kyoto University, School of Medicine, Research Investigator, 医学研究科, 研究員 (70362514)
SUZUKI Satoshi  Akita University, School of Medicine, Professor, 医学部, 教授 (10311565)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2005: ¥10,300,000 (Direct Cost: ¥10,300,000)
KeywordsES cells / Metabolic syndome / Hormone / Endothelial cells / Vascular smooth muscle cells / Adipocytes / Regeneration medicine / Adrenomedullin / アドレメジュリン / Notch / VEGF / cAMP / 動脈 / 血管
Research Abstract

This project was conducted to delineate the cell differentiation pathways involved in the pathogenesis of metabolic syndrome, that is, the differentiation pathway of mesenchymal cells ; vascular cells (endothelial cells and vascular smooth muscle cells), adipocytes and skeletal muscle cells, and examined the possibility of the re-differentiation therapy for metabolic syndrome, using human ES cells.
We established the culture methods to differentiate vascular cells, osteocytes/chondrocytes and adipocytes, using human ES cells and traced the cell surface marker expressions in these cells. Adrenomedullin (AM), the vasodilator hormones, was shown to augment endothelial differentiation of human ES cell-derived vascular progenitor cells (VPC). AM was further demonstrated to induce arterialization of ES cell-derived endothelial cells through Notch signaling pathway. We also reported that AM was expressed highly in adipocytes and co-culture of adipocytes and ES cell-derived VPC resulted in endothelial cell differentiation.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (37 results)

All 2007 2006 2005 Other

All Journal Article (36 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9.2007

    • Author(s)
      Yokota K. et al.
    • Journal Title

      J Biol Chem. 282(3)

      Pages: 1998-2010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column.2007

    • Author(s)
      Iigaya K.. et al.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 292(2)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovaseularization2007

    • Author(s)
      Shingo S. et al.
    • Journal Title

      Investigative Ophthalmology & Visual science 48(1)

      Pages: 422-429

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Add-on amlodipine improves arterial function and structure in hypertensive patients treated with an angiotensin receptor blocker2007

    • Author(s)
      Ichihara A. et al.
    • Journal Title

      J Cardiovasc Pharmacol 49(3)

      Pages: 161-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc92007

    • Author(s)
      Yokota K. et al.
    • Journal Title

      J Biol Chem. 282

      Pages: 1998-2010

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column2007

    • Author(s)
      ligaya K.. et al.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 292

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovascularization2007

    • Author(s)
      Shingo S. et al.
    • Journal Title

      Investigative Ophthalmology & Visual Science48

      Pages: 422-429

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Add-on amlodipine improves arterial function and structure in hypertensive patients treated with an angiotensin receptor blocker2007

    • Author(s)
      Ichihara A. et al.
    • Journal Title

      J Cardiovasc Pharmacol 49

      Pages: 161-166

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovascularization2007

    • Author(s)
      Shingo S. et al.
    • Journal Title

      Investigative Ophthalmology & Visual science 48(1)

      Pages: 422-429

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The neuron-protective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential.2006

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

      Endocrinology 147

      Pages: 1642-1653

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Benefits of candesartan on arterial and renal damage of non-diabetic hypertensive patients treated with calcium channel blockers2006

    • Author(s)
      Ichihara A. et al.
    • Journal Title

      Am J Nephrol. 26(5)

      Pages: 462-468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors2006

    • Author(s)
      Yurugi-Kobayashi T. et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol 26(9)

      Pages: 1977-1984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Benefits of candesartan on arterial and renal damage of non-diabetic hypertensive patients treated with calcium channel blockers2006

    • Author(s)
      Ichihara A. et al.
    • Journal Title

      Am J Nephrol. 26

      Pages: 462-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors2006

    • Author(s)
      Yurugi-Kobayashi T. et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol 26

      Pages: 1977-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors2006

    • Author(s)
      Yurugi-Kobayashi T. et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 26(9)

      Pages: 1977-84

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Therapeutic potential of thiazolidinediones in activation of peroxisome proliferators-activated receptor γ for monocyte recruitment and endothelial regeneration.2005

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

      Eur. J. Pharmacol. 508

      Pages: 255-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II suppresses growth-arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK).2005

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

      Regul. Pept. 127

      Pages: 159-167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagons promoter-ghrelin transgenic mice2005

    • Author(s)
      H.Iwakura, et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 15247-15256

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading.2005

    • Author(s)
      H.Huang, et al.
    • Journal Title

      J. Artif. Organs 8

      Pages: 110-118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis.2005

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

      Genes & Development 19

      Pages: 2054-2065

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Papillary thyroid carcinoma without metastases manifesting as an autonomously functioning thyroid nodule.2005

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

      Endocrine Journal 52

      Pages: 309-316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression of the adrenomedullin gene in adipose tissue.2005

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

      Regul. Pept. 132

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Therapeutic potential of thiazolidinediones in activation of peroxisome proliferators-activated receptor γ for monocyte recruitment and endothelial regeneration2005

    • Author(s)
      T.Tanaka et al.
    • Journal Title

      Eur. J. Pharmacol. 508

      Pages: 255-265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II suppresses growth-arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK).2005

    • Author(s)
      T.Saito et al.
    • Journal Title

      Regul. Pept. I 27

      Pages: 159-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagons promoter-ghrelin transgenic mice.2005

    • Author(s)
      H.Iwakura et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 15247-15256

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading.2005

    • Author(s)
      H.Huang et al.
    • Journal Title

      J. Artif. Organs 8

      Pages: 110-118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis.2005

    • Author(s)
      K.Hamada et al.
    • Journal Title

      Genes & Development 19

      Pages: 2054-2065

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Papillary thyroid carcinoma without metastases manifesting as an autonomously functioning thyroid nodule2005

    • Author(s)
      T.Majima et al.
    • Journal Title

      Endocrine Journal 52

      Pages: 309-316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of the adrenomedullin gene in adipose tissue.2005

    • Author(s)
      T.Nambu et al.
    • Journal Title

      Regul. Pept. 132

      Pages: 17-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Therapeutic potential of thiazolidinediones in activation of peroxisome proliferaxors-activated receptor γ for monocyte recruitment and endothelial regeneration.2005

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

      Eur.J.Pharmacol. 508

      Pages: 255-265

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Angiotensin II suppresses growth-arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase(MAPK).2005

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

      Regul.Pept. 127

      Pages: 159-167

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagons promoter-ghrelin transgenic mice.2005

    • Author(s)
      H.Iwakura, et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 15247-15256

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differentiation from embryonic stem cells to vascular wall cells under in vitro nulsatile flow loading.2005

    • Author(s)
      H.Huang, et al.
    • Journal Title

      J.Artif.Organs 8

      Pages: 110-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis.2005

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

      Genes & Development 19

      Pages: 2054-2065

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of the adrenomedullin gene in adipose tissue.2005

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

      Regul.Pept. 132

      Pages: 17-22

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The neuron-protective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential

    • Author(s)
      K.Miyashita et al.
    • Journal Title

      Endocrinology 147

      Pages: 1642-1653

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] グアニル酸シクラーゼAを活性化する薬剤の脂肪肝改善作用2006

    • Inventor(s)
      中尾一和, 伊藤 裕, 宮下和季
    • Industrial Property Rights Holder
      中尾一和, 伊藤 裕, 宮下和季
    • Industrial Property Number
      2006-250529
    • Filing Date
      2006-09-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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