Temporal gradient in sheer-induced signaling pathway:: involvement of MAP kinase, c-fos, and connexin43
Temporal gradient in sheer-induced signaling pathway:: involvement of MAP kinase, c-fos, and connexin43
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DOI：
10.1152/ajpheart.2000.278.5.h1598
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发表时间：
2000-05-01
影响因子：
4.8
通讯作者：
Frangos, JA
中科院分区：
文献类型：
--
作者：
Bao, XP;Clark, CB;Frangos, JA
研究了剪切力和稳态剪切力的时间梯度对人内皮细胞中细胞外信号调节蛋白激酶1和2（ERK 1/ERK 2）、c-fos和连接蛋白43（Cx43）活性的影响。使用三种层流剖面（16 dyn/cm（2）），包括脉冲流（剪切应力突然施加3 s）、斜坡流（剪切应力在流动开始时平滑过渡）和阶梯流（剪切应力在流动开始时突然施加）。相对于静态对照，脉冲流刺激ERK 1/ERK 2的磷酸化8.5- 7.5倍，分别在10分钟，以及c-fos的mRNA表达51倍，在30分钟，和Cx43的8倍，在90分钟。这些高水平的mRNA表达持续至少4小时。相反，斜坡流不能显著诱导基因表达，甚至抑制ERK 1/ERK 2的活化。阶梯流，其中包含一个尖锐的时间梯度的剪切应力和一个稳定的剪切分量，只引起中度和短暂的反应，表明这些流体剪切刺激在内皮细胞信号转导的独特作用。丝裂原活化蛋白激酶激酶的特异性抑制剂PD-98059抑制脉冲流诱导的c-fos和Cx43 mRNA表达。因此，这些研究结果暗示参与ERK 1/ERK 2，c-fos，和Cx43的信号转导途径诱导的时间梯度剪切。
The effect of a temporal gradient in shear and steady shear on the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/ERK2), c-fos, and connexin43 (Cx43) in human endothelial cells was investigated. Three laminar flow profiles (16 dyn/cm(2)), including impulse flow (shear stress abruptly applied for 3 s), ramp flow (shear stress smoothly transitioned at flow onset), and step flow (shear stress abruptly applied at flow onset) were utilized. Relative to static controls, impulse flow stimulated the phosphorylation of ERK1/ERK2 8.5- to 7.5-fold, respectively at 10 min, as well as the mRNA expression of c-fos 51-fold at 30 min, and Cx43 8-fold at 90 min. These high levels of mRNA expression were sustained for at least 4 h. in contrast, ramp flow was unable to significantly induce gene expression and even inhibited the activation of ERK1/ERK2. Step flow which contains both a sharp temporal gradient in shear stress and a steady shear component, elicited only moderate and transient responses, indicating the distinct role of these fluid shear stimuli in endothelial signal transduction. The specific inhibitor of mitogen-activated protein kinase kinase PD-98059 inhibited impulse flow-induced c-fos and Cx43 mRNA expression. Thus these findings implicate the involvement of ERK1/ERK2, c-fos, and Cx43 in the signaling pathway induced by the temporal gradient in shear.