Role of angiotensin and the clock system in the circadian regulation of plasminogen activator inhibitor-1.
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.
Masuda
Yoko
Y
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Emoto
Noriaki
N
Nonaka
Hidemi
H
Yagita
Kazuhiro
K
Todo
Takeshi
T
Okamura
Hitoshi
H
Yokoyama
Mitsuhiro
M
Hirata
Ken-ichi
K
D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002940:Circadian Rhythm; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System; D015398:Signal Transduction
D000809:Angiotensins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1