Clock upregulates intercellular adhesion molecule-1 expression and promotes mononuclear cells adhesion to endothelial cells
Clock upregulates intercellular adhesion molecule-1 expression and promotes mononuclear cells adhesion to endothelial cells
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时钟上调细胞间粘附分子1的表达并促进单核细胞与内皮细胞的粘附
DOI：
10.1016/j.bbrc.2013.12.022
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发表时间：
2014-01-10
影响因子：
3.1
通讯作者：
Qian, Ruizhe
中科院分区：
文献类型：
--
作者：
Gao, Yinghua;Meng, Dan;Qian, Ruizhe
生物钟是一种基本的螺旋-环-螺旋（bHLH）转录因子，在生理功能的昼夜节律中起重要作用。以往的研究表明，细胞间粘附分子-1（ICAM-1）在Clock突变小鼠肝组织中的表达减少。然而，Clock如何调节ICAM-1的表达以及Clock是否影响细胞粘附功能仍不清楚。在本研究中，我们发现外源性Clock表达上调了小鼠脑微血管内皮细胞系中ICAM-1和其他粘附相关基因包括VCAM 1和CCL-2的基因表达，并增加了ICAM-1的转录活性。相反，Clock的缺失降低了这些基因的表达和ICAM-1的转录活性。染色质免疫沉淀（ChIP）分析显示Clock与ICAM-1基因的E-box样增强子结合。ICAM-1基因在血清休克后的内皮细胞中呈节律性表达，提示ICAM-1可能是一种钟控基因。Clock通过ICAM-1调节单核细胞与内皮细胞的粘附。总之，我们的研究结果表明Clock是ICAM-1的正调节剂，并促进单核细胞与内皮细胞的粘附。(C)2013 Elsevier Inc. All rights reserved.
Clock is a basic helix-loop-helix (bHLH) transcription factor that plays important role in circadian rhythms of various physiological functions. Previous study showed that the expression of intercellular adhesion molecule-1 (ICAM-1) was reduced in the liver tissues of Clock mutant mice. However, how Clock regulates ICAM-1 expression and whether Clock affects cell adhesion function remain unknown. In the present study, we found that exogenous expression of Clock upregulated the gene expressions of ICAM-1 and other adhesion-related genes including VCAM1 and CCL-2, and increased the transcriptional activity of ICAM-1 in mouse brain microvascular endothelial cell lines. In contrast, loss of Clock decreased these gene expressions and ICAM-1 transcriptional activity. Chromatin immunoprecipitation (ChIP) assay revealed that Clock binds to the E-box-like enhancer of ICAM-1 gene. ICAM-1 gene showed rhythmic expression in endothelial cells after serum shock in vitro, suggesting ICAM-1 may be a Clock-controlled gene. Clock regulates the adhesion of mononuclear cells to endothelial cells via ICAM-1. Together, our findings show that Clock is a positive regulator of ICAM-1, and promotes the adhesion of mononuclear cells to endothelial cells. (C) 2013 Elsevier Inc. All rights reserved.