期刊
BIOCHEMICAL PHARMACOLOGY
卷 77, 期 2, 页码 196-203出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2008.10.014
关键词
Rho-kinase inhibitor; TGF-beta; MAP kinase; VEGF; Osteoblast
资金
- Ministry of Education, Science, Sports and Culture of Japan [16590873, 16591482]
- Ministry of Health, Labour and Welfare of Japan
- The Foundation for Growth Science
- Grants-in-Aid for Scientific Research [16590873, 16591482] Funding Source: KAKEN
We have previously reported that transforming growth factor-beta (TGF-beta) stimulates the synthesis of vascular endothelial growth factor (VEGF) through p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. in order to investigate whether Rho-kinase is involved in the TGF-beta-stimulated VEGF synthesis in these cells we examined the effects of Rho-kinase inhibitors on the VEGF synthesis. TGF-beta time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1) which is a well known substrate of Rho-kinase. Y27632 and fasudil, Rho-kinase inhibitors, significantly reduced the TGF-beta-stimulated VEGF synthesis as well as the MYPT-1 phosphorylation. Y27632 and fasudil failed to affect the TGF-beta-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or Smad2. On the contrary, Y27632 as well as fasudil markedly suppressed the TGF-beta-induced phosphorylation of SAPK/JNK. Taken together, our results strongly suggest that Rho-kinase regulates TGF-beta-stimulated VEGF synthesis via SAPK/JNK activation in osteoblasts. (C) 2008 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据