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Inhibition of the binding of basic fibroblast growth factor to its receptor and angiogenesis by synthetic peptides related to platelet factor 4

Research Project

Project/Area Number 03670629
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY
OITA MEDICAL UNIVERSITY

Principal Investigator

SATO Yasufumi (1993)  Oita Medical University, First Department of Internal Medicine, Research Associate, 医学部, 助手 (50178779)

ICHIMIYA Hitoshi (1992)  KYUSHU UNIVERSITY FACULTY OF MEDICINE Assistant Professor, 医学部, 助手 (10183170)

牧野 剛緒 (1991)  九州大学, 医学部, 助手 (30219307)

Co-Investigator(Kenkyū-buntansha) SATOH Hiroshi  KYUSHU UNIVERSITY FACULTY OF MEDICINE Assistant Professor, 医学部, 助手
CHIJIIWA Kazuo  KYUSHU UNIVERSITY FACULTY OF MEDICINE Lecturer, 医学部, 講師 (90179945)
一宮 仁  九州大学, 医学部, 助手 (10183170)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsplatelet factor 4(PF-4) / basic fibroblast growth factor(BFGF) / angiogenesis / heparin binding / synthetic peptide / FK506 / Liver Regeneration / Hepatectomy / Protein Content / DNA Content / DNA Synthesis / Liver Enzyme
Research Abstract

We have found that platelet factor 4 (PF-4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor and inhibits the spontaneous tube formation of endothelial cells in type 1 collagen gel (in vitro angiogenesis). These biological activities localize at the carboxyl-terminal heparin binding domain of the PF-4 molecule. A synthetic peptide composed with at least 10 amino acids (KKIIKKLLES : C-10) of carboxyl terminal PF-4 retains these activities. It is speculated that the cluster of basic amino acids, lysine, plays an important role, In order to obtain an active synthetic peptide with minimal amino acids, we composed KKIIKK (C-6) and compared its activities with that of C-10. We could not observe any biological activities in C-6. Therefore, not only electric charges but also three-dimensional structure of the peptide might be important to express its activity. Finally, we tested the in vivo effect of C-10 whether or not it blocked angiogenesis after the inoculation of tumor cells in mice. C-10 had no significant effect on angiogenesis induced by tumor cells. These results indicates that multiple factors may be involved in tumor angiogenesis, and the elimination of the effect of bFGF may not be sufficient.

Report

(4 results)
  • 1993 Final Research Report Summary
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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