Masuda Yoko, Emoto Noriaki, Nonaka Hidemi, Yagita Kazuhiro, Todo Takeshi, Okamura Hitoshi, Yokoyama Mitsuhiro, Hirata Ken-ichi
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Kobe J Med Sci. 2009 Mar 31;54(6):E264-71.
The clock system and the renin-angiotensin system (RAS) have been reported to play an important role in the circadian expression of plasminogen activator inhibitor-1 (PAI-1) gene. However, the degree of involvement of these systems remains unknown. In the present study, we investigated the roles of the clock system and the RAS in the circadian expression of PAI-1 in the peripheral tissues in vivo by using Cry1/Cry2 double knockout (Cry1/2-deficient) and angiotensin type 1 (AT1a) receptor knockout (AT1a-deficient) mice. We observed no significant rhythmicity in the PAI-1 expression in all tissues examined in Cry1/2-deficient mice; this suggests that the clock system is indispensable for the circadian expression of PAI-1. In AT1a-deficient mice, apparent circadian oscillation of PAI-1 expression was observed in the lung and liver but not in the kidney, suggesting that AT1a-mediated signaling modulates the circadian expression of PAI-1 in a tissue-specific manner.
据报道，时钟系统和肾素-血管紧张素系统（RAS）在纤溶酶原激活物抑制剂-1（PAI-1）基因的昼夜节律表达中起重要作用。然而，这些系统的参与程度尚不清楚。在本研究中，我们通过使用Cry1/Cry2双敲除（Cry1/2缺陷）和血管紧张素1型（AT1a）受体敲除（AT1a缺陷）小鼠，研究了时钟系统和RAS在体内外周组织中PAI-1昼夜节律表达中的作用。我们在Cry1/2缺陷小鼠的所有检测组织中均未观察到PAI-1表达的明显节律性；这表明时钟系统对于PAI-1的昼夜节律表达是不可或缺的。在AT1a缺陷小鼠中，在肺和肝脏中观察到了PAI-1表达的明显昼夜振荡，但在肾脏中未观察到，这表明AT1a介导的信号以组织特异性方式调节PAI-1的昼夜节律表达。
