Purinergic signaling is required for fluid shear stress-induced NF-κB translocation in osteoblasts.
Purinergic signaling is required for fluid shear stress-induced NF-κB translocation in osteoblasts.
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DOI：
10.1016/j.yexcr.2011.01.007
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发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
Duncan RL
中科院分区：
文献类型：
--
作者：
Genetos DC;Karin NJ;Geist DJ;Donahue HJ;Duncan RL
流体剪切力调节成骨细胞中的基因表达，部分是通过激活转录因子NF-κB。我们研究了这一过程是否受嘌呤受体激活的控制。在静态条件下，成骨细胞表达NF-κB抑制蛋白I-κBα，并呈胞浆定位；在流体剪切力作用下，I-κBα水平降低，并出现核内定位。在三磷酸腺苷耗竭的培养液中，暴露于流体剪切力的细胞内的I-κBα没有显著降低，而核因子-κB仍留在胞浆内。使用氧化型三磷酸腺苷或亮蓝G，P2X7受体拮抗剂也得到了类似的结果，表明P2X7受体参与了流体切应力诱导的IκBα降解和NF-κB的核积聚。药物阻断P2Y6受体也可以阻止剪切诱导的IκBα降解。这些现象既不涉及ERK1/2信号，也不涉及由P2X7产生的溶血磷脂酸激活的自分泌。我们的结果提示，流体切应力通过P2Y6和P2X7受体调节NF-κB的活性。
Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-κB. We examined whether this process was under control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-κB inhibitory protein IκBα and exhibited cytosolic localization of NF-κB. Under fluid shear stress, IκBα levels decreased, and concomitant nuclear localization of NF-κB was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in IκBα, and NF-κB remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X7 receptor antagonists, indicating that the P2X7 receptor is responsible for fluid shear-stress-induced IκBα degradation and nuclear accumulation of NF-κB. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced IκBα degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X7-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-κB activity through the P2Y6 and P2X7 receptor.
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