Involvement of p38 MAP kinase in TGF‐β‐stimulated VEGF synthesis in aortic smooth muscle cells

Involvement of p38 MAP kinase in TGF‐β‐stimulated VEGF synthesis in aortic smooth muscle cells
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p38 MAP 激酶参与 TGF-β-刺激主动脉平滑肌细胞中 VEGF 的合成

DOI:
10.1002/jcb.1179
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发表时间:
2001
影响因子:
4
通讯作者:
Toshihiko Uematsu
Toshihiko Uematsu
中科院分区:
生物学2区
文献类型:
--
作者:
Takuji Yamamoto;O. Kozawa;K. Tanabe;Shigeru Akamatsu;H. Matsuno;Shuji Dohi;Toshihiko Uematsu

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尽管已知转化生长因子-β可诱导血管平滑肌细胞合成血管内皮细胞生长因子,但其机制尚不清楚。在本研究中,我们研究了丝裂原活化蛋白(MAP)激酶超家族是否参与了转化生长因子-β刺激的血管内皮细胞生长因子的合成。转化生长因子-β可促进p42/p44和p38蛋白激酶的磷酸化,但对应激激活蛋白激酶/c-jun氨基末端蛋白激酶的磷酸化无明显影响。转化生长因子-β诱导的血管内皮生长因子合成不受上游激活p42/p44蛋白激酶的特异性抑制剂PD98059或U0126的影响。我们证实PD98059或U0126确实能抑制转化生长因子-β对p42/p44蛋白激酶的磷酸化。P38MAP的特异性抑制剂PD169316和SB203580可显著抑制转化生长因子-β刺激的血管内皮生长因子的合成(均呈剂量依赖关系)。PD169316或SB203580可减弱转化生长因子-β诱导的p38MAPK的磷酸化。这些结果有力地提示,p38MAPK参与了转化生长因子-β刺激血管内皮细胞合成血管内皮生长因子的途径。J.细胞。生物化学。82:591-598,2001。©2001 Wiley-Liss公司
Although it is known that transforming growth factor (TGF)‐β induces vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells, the underlying mechanisms are still poorly understood. In the present study, we examined whether the mitogen‐activated protein (MAP) kinase superfamily is involved in TGF‐β‐stimulated VEGF synthesis in aortic smooth muscle A10 cells. TGF‐β stimulated the phosphorylation of p42/p44 MAP kinase and p38 MAP kinase, but not that of SAPK (stress‐activated protein kinase)/JNK (c‐Jun N‐terminal kinase). The VEGF synthesis induced by TGF‐β was not affected by PD98059 or U0126, specific inhibitors of the upstream kinase that activates p42/p44 MAP kinase. We confirmed that PD98059 or U0126 did actually suppress the phosphorylation of p42/p44 MAP kinase by TGF‐β in our preparations. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the TGF‐β‐stimulated synthesis of VEGF (each in a dose‐dependent manner). PD169316 or SB203580 attenuated the TGF‐β‐induced phosphorylation of p38 MAP kinase. These results strongly suggest that p38 MAP kinase plays a part in the pathway by which TGF‐β stimulates the synthesis of VEGF in aortic smooth muscle cells. J. Cell. Biochem. 82: 591–598, 2001. © 2001 Wiley‐Liss, Inc.
DOI: 10.1097/00006982-199515020-00024
发表时间: 1994
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