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

2003 Fiscal Year Final Research Report Summary

Clinical Application of Hepatocyte Growth Factor (HGF) to cardiovascular disease: Its molecular mechanisms and possibility of molecular therapy.

Research Project

Project/Area Number 13557065
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

MORISHITA Yuichi  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 寄附講座教員(客員教授) (40291439)

Co-Investigator(Kenkyū-buntansha) TAIJI Matsuo  Sumitomo Pharmaceuticals Co., Ltd., Research Division Discovery Research Laboratories, Research Scientist, 主任研究員
MATSUMOTO Kunio  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90201780)
Project Period (FY) 2001 – 2003
KeywordsHGF / Ischemic heart disease / Endothelial cell / Celebralinfection / Gene Therapy / Peripheral arterial disease / Angiogenesis / Apoptosis
Research Abstract

1)Molecular mechanisms of HGF in regulation of vascular endothelial cells.
This study demonstrated that HGF is not only growth factor but potent protector of endothelial cells. Endothelial cell death induced by high-glucose condition was inhibited by addition of HGF through the suppression of activation of caspase 3. Also, it was suggested that inhibition of cell death was mediated by up-regulation of bcl-xL and bcl-2.
2)HGF-based gene therapy for ischemic diseases.
We performed clinical gene therapy for peripheral arterial disease using HGF. Intramuscular injection of naked HGF plasmid is safe, feasible and can achieve successful improvement of ischemic limbs. Further clinical studies of alternative dosing regimens of gene therapy with randomized placebo-controlled trials will be required to define the efficacy of this therapy.
Also, to evaluate the effect of HGF on ischemic heart disease, we employed NOGA system and demonstrated that gene transfer of HGF into myocardium resulted in increase in myocardial blood flow and decrease in ischemic area.
3)Application of HGF to treatment for cerebral infarction.
We demonstrated that gene transfer of HGF into ischemic brain resulted in suppression of neuron cell death and increase in blood supply as compared to that of control. Moreover, pre-treatment by trans-gene of HGF before Hgation decreased infracted area and improved behavior, suggesting its possibility of gene therapy for cerebral infarction.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Nakagami H et al.: "Anti-apopototic action of hepatocyte growth factor through mitogen-atcivate protein kinase on human aortic endothelial cells."Journal of Hypertention. 18. 1411-1420 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagami H et al.: "Phosphorylation of p38 Mitogen - Activated Protein Kinase Downstream of Bax-Caspase-3 Pathway Leads to Cell Death induced by High D-Glucose In Human."Diabetes. 50. 1472-1481 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y et al.: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbithindlimb ischemia models : preclinical study for treatment of perpheral arterial disease."Gene Therapy. 8. 181-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y et al.: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model : molecular mechanisms of delayed angiogenesis in diabetes."Circulation. Nov 6 104(19). 2344-2350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y et al.: "Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy."Hypertension. Jul;401. 47-53 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakabayashi M et al.: "HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model."Diabetologia. 46. 115-123 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morishita R et al.: "Gene Therapy and Regulation"VSP. (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagami H. et al.: "Anti-apopototic action of hepatocyte growth factor through mitogen-activate protein kinase on human aortic endothelial cells."Journal of Hypertention. 18. 1411-1420 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakagami H. et al.: "Phosphorylation of p38 Mitogen -Activated Protein Kinase Downstream of Bax-Caspase-3 Pathway Leads to Cell Death induced by High D-Glucose in Human."Diabetes. 50. 1472-1481 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniyama Y. et al.: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbithindlimb ischemia models: preclinical study for treatment of perpheral arterial disease."Gene Therapy. 8. 181-189 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniyama Y. et al.: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes."Circulation. Nov. 6 104(19). 2344-2350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniyama Y. et al.: "Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy."Hypertension. July ; 40, 1. 47-53 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakabayashi M. et al.: "HGF/NK4 inhibited VEGF-induced angiogenesis in invitro cultured endothelial cells and in vivo rabbit model."Diabetologia. Vol46. 115-123 (2003)

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

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi