| Budget Amount *help |
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 2003 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 2002 : ¥1,900,000 (Direct Cost : ¥1,900,000)
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| 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.
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