title: Clock upregulates intercellular adhesion molecule-1 expression and promotes mononuclear cells adhesion to endothelial cells.
abstract: 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.
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Yinghua
authors: Y
authors: Gao
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Dan
authors: D
authors: Meng
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Ning
authors: N
authors: Sun
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Zhu
authors: Z
authors: Zhu
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Ran
authors: R
authors: Zhao
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Chao
authors: C
authors: Lu
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China.
authors: Sifeng
authors: S
authors: Chen
authors: Department of Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, PR China.
authors: Luchun
authors: L
authors: Hua
authors: Department of Physiology and Pathophysiology, Shanghai Medical College Fudan University, Shanghai 200032, PR China. Electronic address: ruizheqian@163.com.
authors: Ruizhe
authors: R
authors: Qian
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D042783:Endothelial Cells / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D051379:Mice; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: Cell adhesion; Clock; Intercellular cell adhesion molecule-1; Transcriptional regulation