Involvement of SAPK/JNK in basic fibroblast growth factor-induced vascular endothelial growth factor release in osteoblasts

被引：49
作者：
Tokuda, H
Hirade, K
Wang, X
Oiso, Y
Kozawa, O [1 ]
机构：
[1] Gifu Univ, Sch Med, Dept Pharmacol, Gifu 5008705, Japan
[2] Chubu Natl Hosp, Natl Inst Longev Sci, Dept Internal Med, Obu, Aichi 4748511, Japan
[3] Nagoya Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi, Japan
来源：
JOURNAL OF ENDOCRINOLOGY | 2003年 / 177卷 / 01期
关键词：
D O I：
10.1677/joe.0.1770101
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
We previously reported that basic fibroblast growth factor (FGF-2) activates p44/p42 nutogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In the present study, we investigated the involvement of stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) in FGF-2-induced VEGF release in these cells. FGF-2 markedly induced the phosphorylation of SAPK/JNK. SP600125, an inhibitor of SAPK/JNK, markedly reduced the FGF-2-induced VEGF release. SP600125 suppressed the FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase induced by FGF-2. PD98059, an inhibitor of upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase, failed to affect the FGF-2-induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the FGF-2-stimulated VEGF release in an additive manner. These results strongly suggest that FGF-2 activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in FGF-2-induced VEGF release.
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页码：101 / 107
页数：7
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