College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Oct 1;49(10):954-961. doi: 10.1093/abbs/gmx084.
In mammals, behavioral and physiological rhythms are controlled by circadian clocks which are entrained by environmental light and food signals. However, how the environmental cues affect digestive tract's circadian clock remains poorly understood. Therefore, in order to elucidate the effect of light cue on the resetting of the peripheral clocks, we investigated the expressions of clock genes (Bmal1, Cry1, Rev-erbα, Per1, and Per2) and digestive function genes (Cck, Cck-1r, Sct, Sctr, and Ctrb1) in the pancreas and duodenum of rats after the light-dark (LD) cycle reversal for 7 days. We found that both the clock genes and digestive function genes exhibited a clear and similar daily rhythmicity in the pancreas and duodenum of rats. After reversal of the LD cycle for 7 days, the expressions of clock genes in pancreas, including Bmal1, Cry1, and Rev-erbα were affected; whereas the expression of Per1 gene failed to fit the cosine wave. However, in the duodenum the shifted genes were Bmal1, Rev-erbα, and Per2; in parallel, the Per1 gene expression also lost its circadian rhythm by reversal of the LD cycle. Therefore, the acrophases of the clock genes were shifted in a tissue- and gene-specific manner. Furthermore, the profiles of the digestive function genes, including Sctr and Ctrb1, were also affected by changes in LD cycle. These observations suggest that the mechanisms underlying the pancreatic and duodenal clocks are distinct, and there may be a potential linkage between the circadian clock system and the digestive system.
在哺乳动物中,行为和生理节律受生物钟控制,生物钟受环境光和食物信号的调节。然而,环境线索如何影响消化道的生物钟仍知之甚少。因此,为了阐明光信号对周围时钟重置的影响,我们研究了时钟基因(Bmal1、Cry1、Rev-erbα、Per1 和 Per2)和消化功能基因(Cck、Cck-1r、Sct、Sctr 和 Ctrb1)在大鼠胰腺和十二指肠中的表达,这些大鼠在经历 7 天的光-暗(LD)循环反转后。我们发现,时钟基因和消化功能基因在大鼠胰腺和十二指肠中均表现出明显且相似的每日节律性。在 LD 循环反转 7 天后,胰腺中时钟基因的表达,包括 Bmal1、Cry1 和 Rev-erbα 受到影响;而 Per1 基因的表达未能适应余弦波。然而,在十二指肠中,移位的基因是 Bmal1、Rev-erbα 和 Per2;同时,Per1 基因的表达也因 LD 循环的反转而失去了昼夜节律。因此,时钟基因的峰相位以组织和基因特异性的方式发生转移。此外,消化功能基因(包括 Sctr 和 Ctrb1)的表达谱也受到 LD 循环变化的影响。这些观察结果表明,胰腺和十二指肠时钟的机制不同,昼夜节律系统与消化系统之间可能存在潜在联系。