Epithelial cell adhesion molecule expression in hepatic stem/progenitor cells is controlled by the molecular clock system
Epithelial cell adhesion molecule expression in hepatic stem/progenitor cells is controlled by the molecular clock system
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DOI：
10.1016/j.bbrc.2018.06.117
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发表时间：
2018-09-05
影响因子：
3.1
通讯作者：
Ohdo, Shigehiro
中科院分区：
文献类型：
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作者：
Kimura, Hinako;Matsunaga, Naoya;Ohdo, Shigehiro
生物钟基因簇在转录水平上控制着生物钟的昼夜节律，调节着人体的各种功能。生物钟基因与多种疾病的病理过程密切相关。虽然有证据表明慢性肝炎患者存在严重的睡眠障碍，但慢性肝炎条件下的肝再生机制及其与时钟基因的关联尚不清楚。在这项研究中，昼夜运动输出周期kaput（CLOCK），这是一个时钟基因，对3，5-二乙氧羰基-1，4-二氢可力丁（DDC）诱导的肝炎动物模型的影响进行了研究。潜在肝干细胞样细胞（上皮细胞粘附分子[EpCAM]阳性细胞）的出现是慢性炎症期间肝再生的初始关键步骤。结果显示，DDC喂养后1周，野生型（WT）小鼠中有相当数量的肝EpCAM阳性细胞。然而，与WT小鼠相比，Clock突变型（Clk/Clk）小鼠中EpCAM阳性细胞的数量减少，并且它们的肝炎更严重。此外，Epcam mRNA的表达，这是一个潜在的肝干细胞样细胞的功能标志物，由LEF 1控制，这是由时钟调节。这项研究的结果将有助于阐明肝再生机制，包括分子水平上的机制，并可能有助于未来开发新的治疗方式。(C)2018爱思唯尔公司All rights reserved.
The circadian rhythm, which regulates various body functions, is transcriptionally controlled by a series of clock gene clusters. The clock genes are related to the pathology of various kinds of diseases. Although there is evidence of serious sleep disorders in patients with chronic hepatitis, the liver regeneration mechanism under chronic hepatitis conditions and its association with the clock genes are not clear. In this study, the influence of the circadian locomotor output cycles kaput (CLOCK), which is one of the clock genes, on a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced hepatitis animal model was investigated. The appearance of potential hepatic stem-like cells (epithelial cell adhesion molecule [EpCAM]-positive cells) is an initial critical step in liver regeneration during chronic inflammation. The results showed a considerable number of hepatic EpCAM-positive cells in the wild-type (WT) mice 1 week after the DDC feeding. However, the number of EpCAM-positive cells in the Clock-mutant (Clk/Clk) mice decreased, and their hepatitis was worse compared with the WT mice. In addition, the expression of Epcam mRNA, which is a functional marker of potential hepatic stem-like cells, was controlled by LEF1, which was regulated by CLOCK. The results of this study will facilitate the elucidation of the liver regeneration mechanisms, including those at the molecular level, and may assist in the development of new treatment modalities in the future. (C) 2018 Elsevier Inc. All rights reserved.