层流剪切力作用下血管内皮细胞内JNK活性的双相性对p53-Mdm2系统动力学的影响

Effect of laminar shear stress-induced a biphasic JNK activity on the p53-Mdm2 dynamics in vascular endothelial cells

最近的实验表明:在层流剪切力作用下,血管内皮细胞内Jun N端激酶(JNK)活性的响应曲线表现出上升或下降的双相特征,然而,目前并不清楚这种双相性如何影响下游的信号网络。该文给出了刻画JNK活性与剪切力关系的解析表达式,并通过一个动力学模型考察了JNK活性的双相性对p53-Mdm2系统的影响。由此发现具有慢速下降相的JNK活性曲线能够驱动较小振幅和较高频率的p53振荡,从而激活有关细胞周期抑制的基因,维护血管的内稳态,防止动脉粥样硬化的产生,可以从JNK活性曲线的特征预测内皮细胞的命运。

Recent experiments have shown that the response curves of Jun N-terminal kinase（JNK） activity exhibit two phases increasing or decreasing by laminar shear stress in vascular endothelial cells. However, how biphasic activity effect the downstream signaling network remains unclear. Here, we speculate an analytical expression characterizing biphasic JNK activity, and investigate the effect of biphasic JNK activity on the p53-Mdm^2 system by a dynamical model. It is found that the JNK activity with slow decrease phase leads the oscillations with smaller amplitude and higher frequency, which may cause the activation of the gene on cell cycle arrest, keepHomeostasis of the blood vessel and prevent atherogenesis in the blood wall exerted by laminar flow. Therefore, perhaps it could be predicted that the endothelial cell fate from the characteristics of JNK activity.