2003 Fiscal Year Final Research Report Summary
Development of novel strategy for targeting of functional proteins into hasement membrance
Project/Area Number |
14580819
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
|
Research Institution | Osaka Univ. |
Principal Investigator |
SHASLIANG Li Osaka Univ., Institute for protein research, Assistant professor, 蛋白質研究所, 助手 (40252720)
|
Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Kiyotoshi Osaka Univ., Institute for protein Research, Professor, 蛋白質研究所, 教授 (50187845)
|
Project Period (FY) |
2002 – 2003
|
Keywords | Basement membrane / lawiain / HGF / bFGF / VEGF |
Research Abstract |
Growth factors bind to various ECM proteins including HSPG, collagen, and fibronectin. However, interaction with LN isoforms remains unknown. In this study, we examined the interaction of three angiogenesis-related growth factors, HGF, bFGF, and VEGF, with LN 1, 2/4, 5, 8, and 10/11 by ELISA. HGF bound preferentially to LN 10/11 and LN 8, and binding was inhibited by heparin, low pH, and heparitinase II treatment. Binding to the 293F cell-expressed LN 10 was weaker than that to LN 10/11 from A549 cells. Mutagenesis studies indicated that HGF-binding sites possibly reside in the short arm of LN 10. Moreover, LN 10/11-bound HGF promoted proliferation of HMEC-1 cells. bFGF also exhibited similar binding preference for LNs, and binding of VEGE to LNs is comparably weak. In conclusion, LN 10/11, rich in blood vessel basement membrane, could capture the angiogenesis-related growth factor such as HGF, bFGF and VEGF with different affinity to promote cell proliferation. These interactions were possibly regulated by such environment factors as heparan sulfate modification and pH change during different physiological or pathological processes.
|
Research Products
(4 results)