College of Biological and Environmental Engineering, Zhejiang University of Technology, Zhaohui Xincun, Hangzhou 310032, China.
J Exp Biol. 2011 Apr 15;214(Pt 8):1257-63. doi: 10.1242/jeb.052100.
Dec1 and Dec2 are regulators of the mammalian molecular clock that show robust circadian rhythms in the suprachiasmatic nucleus and various peripheral tissues. Although the expression of Dec1 and Dec2 is altered by multiple stimuli in different organs, their transcriptional regulatory mechanisms have not been fully elucidated for the kidney. In the present study, we describe for the first time significant dissociation of expression patterns with arrhythmic expression of Dec1 and rhythmic expression of Dec2 in rat kidney under a normal light-dark (LD) cycle. Daytime restricted feeding (RF) significantly altered the expression patterns of these two clock genes, and even induced circadian expression of Dec1 with an amplitude of 2.2 on day 3 and 4.2 on day 7. However, when a reversed feeding schedule was coupled with a reversed LD cycle, the expression of Dec1 but not Dec2 reverted to being arrhythmic. Moreover, exogenous injection of the glucocorticoid analogue dexamethasone (Dex) at certain times of the day resulted in rhythmic expression of Dec1, which was similar to that seen following RF for 7 days. In contrast, endogenous disruption of glucocorticoids by adrenalectomy abolished RF-induced rhythmic expression of Dec1 in the kidney. These observations suggest the existence of a glucocorticoid gating mechanism in the circadian expression of Dec1 in rat kidney.
Dec1 和 Dec2 是哺乳动物分子钟的调节剂，在视交叉上核和各种外周组织中表现出强大的昼夜节律。尽管 Dec1 和 Dec2 的表达在不同器官中受到多种刺激的影响，但它们在肾脏中的转录调节机制尚未完全阐明。在本研究中，我们首次描述了在正常光-暗（LD）周期下，大鼠肾脏中 Dec1 呈现非节律性表达，而 Dec2 呈现节律性表达的显著分离表达模式。限时喂养（RF）显著改变了这两个生物钟基因的表达模式，甚至在第 3 天和第 7 天诱导 Dec1 的昼夜表达，幅度分别为 2.2 和 4.2。然而，当反向喂养方案与反向 LD 周期相结合时，Dec1 的表达而非 Dec2 的表达恢复为非节律性。此外，在一天中的特定时间点注射糖皮质激素类似物地塞米松（Dex）会导致 Dec1 的节律性表达，这与连续 7 天 RF 后的情况相似。相比之下，通过肾上腺切除术破坏内源性糖皮质激素会消除 RF 诱导的肾脏中 Dec1 的节律性表达。这些观察结果表明，在大鼠肾脏中 Dec1 的昼夜表达存在糖皮质激素门控机制。
