1995 Fiscal Year Final Research Report Summary
Difference in physiological roles of phosphorylated and non-phosphorylated rat fetuin.
| Project/Area Number |
06454524
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
DAIKUHARA Yasushi Kagoshima University Dental School, Professor, 歯学部, 教授 (40028733)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Osamu Kagoshima University Dental School, Research, Associate, 歯学部, 助手 (70128445)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Fetuin / Phosphorylated fetuin / Non-phosphorylated fetuin / alpha_2-HS glycoprotein / Hepatocyte growth factor (HGF) / Parathyroid hormone / Bone resorption / Chalone |
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| Research Abstract |
In this project, we obtained following results.
1. Rat fetuin synthesized and secreted by hepatocytes was phosphorylated form and the rate of biosynthesis of this phosphorylated fetuin (phosphofetuin) was suppressed by inflammatory cytokines such as IL-1 (alpha and beta) and TNF-alpha, but it was stimulated by growth factors to hepatocytes such as hepatocyte growth factor (HGF), epidermal growth factor and insulin. This regulation of biosynthesis of phosphofetuin was confirmed both by the levels of protein and mRNA.
2. Phosphofetuin suppressed the biological activity of HGF which is known to be a potent mitogen to hepatocytes. However, non-phosphorylated fetuin did not show the activity to suppress the HGF activity. For the mechanism how phosphofetuin suppress the HGF activity, we found that phosphofetuin has affinity to bound HGF and thus phosphofetuin interfered with HGF binding to its specific receptor, c-Met. These observation suggest that phosphofetuin synthesized by hepatocytes may be a natural modulator of HGF as a 7chalone'.
3. Non-phosphorylated rat fetuin enhanced bone resorption induced by low concentrations (0.1-0.5nM) of parathyroid hormone (PTH), as measured by release of ^<45>Ca from ^<45>Ca-prelabeled rat radius, but it had no activity on bone resorption without PTH.We also found that rat non-phosphorylated fetuin enhanced the digestion of type I collagen by cathepsin L.
4. Although bovine fetuin and its human counterpart of alpha_2-HS glycoprotein is known to be a plasma sialoprotein for long time, its physiological role is not yet clear. From above observations using rat fetuin, we found one of physiological roles of phosphorylated and non-phosphorylated fetuin/alpha_2-HS glycoprotein.
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