Mouse intestinal cryptdins exhibit circadian oscillation

Mouse intestinal cryptdins exhibit circadian oscillation
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DOI:
10.1096/fj.05-4216fje
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发表时间:
2005-08-01
期刊:
影响因子:
4.8
通讯作者:
Miskin, R
Miskin, R
中科院分区:
生物学2区
文献类型:
--
作者:
Froy, O;Chapnik, N;Miskin, R

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先天免疫利用大量的抗菌多肽,即防御素,来对抗摄入的细菌。小鼠肠道防御素(隐肽)是组成性产生和分泌的,但在感染和/或炎症的情况下过度表达。我们的目的是确定在健康条件下生物钟是否在cryptdin表达中发挥作用。分析FVB/N小鼠小肠回肠和空肠中cryptdin 1和cryptdin 4在昼夜周期内的表达,发现振荡在暗期结束时达到峰值。为了消除cryptdin振荡源于食物摄入的可能性,我们分析了禁食条件下cryptdin的表达,发现振荡,但有3小时的相移。比较两种小鼠品系(C57BL/6 vs. FVB/N)的cryptdin表达,发现C57BL/6的表达水平较高,C57BL/6是一种对肠道感染高度敏感的小鼠品系,很可能是由于cryptdin成熟受损。本研究结果表明,生物钟参与调节小肠中cryptdin的表达,并增强食物作为授时因子(同步器)的能力。假设在人类中也有类似的控制,我们的结果可能意味着防御素的表达在白天达到高峰。
The innate immunity utilizes a plethora of antibacterial polypeptides, known as defensins, to combat ingested bacteria. Mouse enteric defensins (cryptdins) are produced and secreted constitutively but are overexpressed in instances of infection and/or inflammation. Our objective was to determine whether the biological clock plays a role in cryptdin expression under healthy conditions. Analysis of cryptdin 1 and cryptdin 4 expression in the ileum and jejunum of the small intestine of FVB/N mice around the circadian cycle revealed oscillation that peaked at the end of the dark phase. To eliminate the possibility that cryptdin oscillation stems from food intake, we analyzed cryptdin expression under fasting conditions and found oscillation but with a 3 h phase-shift. Comparison of cryptdin expression in two mouse strains (C57BL/6 vs. FVB/N) revealed higher levels in C57BL/6, a mouse strain that is highly susceptible to enteric infection, due, most likely, to impaired cryptdin maturation. The results of this study indicate the involvement of the biological clock in regulating cryptdin expression in the small intestine and reinforce the capacity of food to act as a zeitgeber (synchronizer). With the assumption of similar control in humans, our results may imply that defensin expression peaks during the day.