Fluid shear stress-induced JNK activity leads to actin remodeling for cell alignment.

Fluid shear stress-induced JNK activity leads to actin remodeling for cell alignment.
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DOI:
10.1002/jcp.22311
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发表时间:
2011-01
影响因子:
5.6
通讯作者:
Lowe-Krentz, Linda
Lowe-Krentz, Linda
中科院分区:
生物学2区
文献类型:
--
作者:
Mengistu, Meron;Brotzman, Hannah;Ghadiali, Samir;Lowe-Krentz, Linda

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流体剪切应力(FSS)作用于内皮细胞表面,通过机械力转导诱导肌动蛋白细胞骨架重塑。本研究的目的是确定是否FSS激活Jun N-末端激酶(JNK),检查空间和时间分布的活性JNK相对于肌动蛋白细胞骨架暴露于不同的FSS条件下的内皮细胞,并评估活性JNK对肌动蛋白重排的影响。暴露于15和20达因/厘米2的FSS诱导更高的活性水平的JNK比低2和4达因/厘米2的流量条件。在较高的FSS治疗,JNK活性增加,增加曝光时间,达到峰值后30分钟流发病与8倍的活性增加相比,静态培养的细胞。FSS诱导的磷酸化JNK与细胞周围的肌动蛋白丝以及应力纤维共定位。药理学阻断JNK活性改变了FSS诱导的肌动蛋白结构和分布作为对FSS的响应。我们的研究结果表明,FSS诱导的肌动蛋白重塑发生在三个阶段,JNK至少在其中一个阶段发挥作用,这表明这种激酶活性参与了从顶端表面到内皮细胞肌动蛋白细胞骨架的机械转导。
Fluid shear stress (FSS) exerted on endothelial cell surfaces induces actin cytoskeleton remodeling through mechanotransduction. This study was designed to determine whether FSS activates Jun N-terminal kinase (JNK), to examine the spatial and temporal distribution of active JNK relative to the actin cytoskeleton in endothelial cells exposed to different FSS conditions, and to evaluate the effects of active JNK on actin realignment. Exposure to 15 and 20 dyn/cm2 FSS induced higher activity levels of JNK than the lower 2 and 4 dyn/cm2 flow conditions. At the higher FSS treatments, JNK activity increased with increasing exposure time, peaking 30 minutes after flow onset with an 8-fold activity increase compared to cells in static culture. FSS-induced phospho-JNK co-localized with actin filaments at cell peripheries, as well as with stress fibers. Pharmacologically blocking JNK activity altered FSS-induced actin structure and distribution as a response to FSS. Our results indicate that FSS-induced actin remodeling occurs in three phases, and that JNK plays a role in at least one, suggesting that this kinase activity is involved in mechanotransduction from the apical surface to the actin cytoskeleton in endothelial cells.
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