Platelet-derived growth factor-BB amplifies PGF2-stimulated VEGF synthesis in osteoblasts: Function of phosphatidylinositol 3-kinase
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説明
We have reported that prostaglandin F2alpha (PGF2alpha) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In addition, we recently showed that phosphatidylinositol 3 (PI3)-kinase activated by platelet-derived growth factor-BB (PDGF-BB) negatively regulates the interleukin-6 synthesis in these cells. In the present study, we investigated the effect of PDGF-BB on the PGF2alpha-induced VEGF synthesis in MC3T3-E1 cells. PDGF-BB, which alone did not affect the levels of VEGF, significantly enhanced the PGF2alpha-stimulated VEGF synthesis. The amplifying effect of PDGF-BB was dose dependent in the range between 10 and 70 ng/ml. LY294002 or wortmannin, specific inhibitors of PI3-kinase, which by itself failed to affect the PGF2alpha-stimulated VEGF synthesis, significantly suppressed the amplification by PDGF-BB. PD98059, a specific inhibitor of MEK1/2, suppressed the amplification by PDGF-BB of the PGF2alpha-stimulated VEGF synthesis similar to the levels of PGF2alpha with PD98059. PDGF-BB itself induced the phosphorylation of p44/p42 MAP kinase in these cells, and the effects of PDGF-BB and PGF2alpha on the phosphorylation of p44/p42 MAP kinase were additive. Moreover, LY294002 had little effect on the phosphorylation of p44/p42 MAP kinase induced by PGF2alpha with PDGF-BB. These results strongly suggest that PGF2alpha-stimulated VEGF synthesis is amplified by PI3-kinase-mediating PDGF-BB signaling in osteoblasts, and that the effect is exerted at a point downstream from p44/p42 MAP kinase.
収録刊行物
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- Prostaglandins, Leukotrienes and Essential Fatty Acids
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Prostaglandins, Leukotrienes and Essential Fatty Acids 77 187-193, 2007-10-01
Elsevier BV
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キーワード
- Flavonoids
- Mitogen-Activated Protein Kinase 1
- Platelet-Derived Growth Factor
- Vascular Endothelial Growth Factor A
- Mitogen-Activated Protein Kinase 3
- Osteoblasts
- Morpholines
- Becaplermin
- Proto-Oncogene Proteins c-sis
- Dinoprost
- Androstadienes
- Mice
- Phosphatidylinositol 3-Kinases
- Chromones
- Animals
- Wortmannin
- Phosphoinositide-3 Kinase Inhibitors