Department of Microbiology, University of Virginia, Charlottesville, Virginia, United States of America.
PLoS One. 2011;6(8):e24338. doi: 10.1371/journal.pone.0024338. Epub 2011 Aug 31.
Endothelial cells in straight, unbranched segments of arteries elongate and align in the direction of flow, a feature which is highly correlated with reduced atherosclerosis in these regions. The mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) is activated by flow and is linked to inflammatory gene expression and apoptosis. We previously showed that JNK activation by flow is mediated by integrins and is observed in cells plated on fibronectin but not on collagen or basement membrane proteins. We now show thatJNK2 activation in response to laminar shear stress is biphasic, with an early peak and a later peak. Activated JNK localizes to focal adhesions at the ends of actin stress fibers, correlates with integrin activation and requires integrin binding to the extracellular matrix. Reducing JNK2 activation by siRNA inhibits alignment in response to shear stress. Cells on collagen, where JNK activity is low, align slowly. These data show that an inflammatory pathway facilitates adaptation to laminar flow, thereby revealing an unexpected connection between adaptation and inflammatory pathways.
动脉中直的、无分支的血管段中的内皮细胞沿血流方向伸长并排列，这一特征与这些区域中动脉粥样硬化的减少高度相关。有丝分裂原激活的蛋白激酶 c-Jun N 末端激酶（JNK）可被血流激活，并与炎症基因表达和细胞凋亡有关。我们之前的研究表明，血流引起的 JNK 激活是由整合素介导的，在铺板于纤维连接蛋白上的细胞中观察到，但在胶原或基底膜蛋白上则观察不到。我们现在发现，层流剪切应力引起的 JNK2 激活呈双相性，有早期峰和晚期峰。活化的 JNK 定位于肌动蛋白应力纤维末端的粘着斑，与整合素的激活相关，需要整合素与细胞外基质的结合。用 siRNA 减少 JNK2 的激活可抑制对剪切应力的排列反应。在胶原上，JNK 活性较低的细胞排列缓慢。这些数据表明，炎症途径有助于适应层流，从而揭示了适应性和炎症途径之间的意外联系。
