Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells
Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells
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DOI：
10.1111/j.1432-0436.2006.00089.x
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发表时间：
2006-12-01
期刊：
影响因子：
2.9
通讯作者：
Chen, Changyi
中科院分区：
文献类型：
--
作者：
Cevallos, Manuel;Riha, Gordon M.;Chen, Changyi
本研究的目的是确定循环应变是否可以促进人脐静脉内皮细胞（HUVECs）表达与成熟平滑肌细胞（SMC）表型相同的标志物，提示内皮细胞向SMC转分化。将HUVEC在拉伸膜上以10%拉伸和60个循环/分钟培养24-96小时，并显示具有增强和组织化的F-肌动蛋白分布的伸长。实时荧光定量PCR检测发现，与静态对照组相比，周期性应变处理的HUVECs中SM 22-α、α-平滑肌肌动蛋白（alpha-SMA）、钙调蛋白1、平滑肌肌球蛋白重链（SMMHC）和钙调蛋白1等5种特异性SMC标志物的mRNA水平显著升高。通过蛋白质印迹和免疫荧光染色，SM 22-alpha和alpha-SMA的蛋白水平也大幅增加。此外，两种特异性内皮标志物，血管性血友病因子（vWF）和血管内皮生长因子受体-2（VEGFR-2），显示mRNA表达减少。此外，当细胞培养回到静态条件时，周期性应变诱导的SM 22-α和α-SMA表达的增加是可逆的。这些结果表明，一个可能的内皮细胞到SMC转分化响应于周期性应变。血流动力学在调节内皮细胞表型中可能在血管系统中起重要作用。
The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were signifcantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-alpha and alpha-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.