Laboratory of Cardiovascular Diseases, West China Hospital, Sichuan University, No.17 Renmin Nanlu 3 Duan, Chengdu, People's Republic of China.
Eur Biophys J. 2012 Jan;41(1):13-25. doi: 10.1007/s00249-011-0752-x. Epub 2011 Oct 12.
We previously demonstrated that CXCR1 and CXCR2 are novel mechanosensors mediating laminar shear-stress-induced endothelial cell (EC) migration (Zeng et al. in Cytokine 53:42-51, 2011). In the present study, an analytical model was proposed to further analyze the underlying mechanisms, assuming the mechanical force (MF) and mechanosensor-mediated biochemical reactions induce cell migration together. Shear stress can regulate both mechanosensor-mediated migration in the flow direction (Ms-M(FD)) and mechanosensor-mediated migration toward a wound (Ms-M(W)). Next, the migration distance, the roles of MF-induced cell migration (MF-M), and the mobilization mechanisms of mechanosensors were analyzed. The results demonstrated that MF-M plays an important role in 15.27 dyn/cm(2) shear-stress-induced EC migration but is far weaker than Ms-M(W) at 5.56 dyn/cm(2). Our findings also indicated that CXCR2 played a primary role, in synergy with CXCR1. The Ms-M(FD) was primarily mediated by the synergistic effect of CXCR1 and CXCR2. In Ms-M(W), when shear stress was beyond a certain threshold, the synergistic effect of CXCR1 and CXCR2 was enhanced, and the effect of CXCR1 was inhibited. Therefore, the retarding of EC migration and wound closure capacity under low shear flow was related to the low magnitude of shear stress, which may contribute to atherogenesis and many other vascular diseases.
我们之前的研究表明，趋化因子受体 1（CXCR1）和趋化因子受体 2（CXCR2）是介导层流剪切应力诱导内皮细胞（EC）迁移的新型机械感受器（Zeng 等人，《细胞因子》53：42-51，2011）。在本研究中，提出了一个分析模型来进一步分析潜在机制，假设机械力（MF）和机械感受器介导的生化反应共同诱导细胞迁移。切应力可以调节沿流方向的机械感受器介导的迁移（Ms-M（FD））和机械感受器介导的向创伤迁移（Ms-M（W））。接下来，分析了迁移距离、MF 诱导的细胞迁移（MF-M）的作用以及机械感受器的动员机制。结果表明，MF-M 在 15.27 dyn/cm(2)的切应力诱导的 EC 迁移中起着重要作用，但在 5.56 dyn/cm(2)时远弱于 Ms-M（W）。我们的研究结果还表明，CXCR2 与 CXCR1 协同作用，起着主要作用。Ms-M（FD）主要由 CXCR1 和 CXCR2 的协同作用介导。在 Ms-M（W）中，当切应力超过一定阈值时，CXCR1 和 CXCR2 的协同作用增强，而 CXCR1 的作用受到抑制。因此，低剪切流下 EC 迁移和创伤闭合能力的延迟与低剪切应力幅度有关，这可能导致动脉粥样硬化和许多其他血管疾病的发生。
