Restricted feeding induces daily expression of clock genes and Pai-1 mRNA in the heart of Clock mutant mice

Plasminogen activator inhibitor-1 (PAI-1) is a key factor of fibrinolytic activity. The activity and mRNA abundance show a daily rhythm. To elucidate the mechanism of daily Pai-1 gene expression, the expression of Pai-1 and several clock genes was examined in the heart of homozygous Clock mutant (Clock/Clock) mice. Damping of the daily oscillation of Pai-1 gene expression in Clock/Clock mice was accompanied with damped or attenuated oscillations of mPer1, mPer2, mBmal1, and mNpas2 mRNA. Daily restricted feeding induced a daily mRNA rhythm of all clock genes and Pai-1 mRNA in Clock/Clock mice as well as wild-type mice. The peaks of clock genes and Pai-1 mRNA were phase-advanced in the heart of both genotypes after 6 days of restricted feeding. The present results demonstrate that daily Pai-1 gene expression depends on clock gene expression in the heart and that a functional Clock gene is not required for restricted feeding-induced resetting of the peripheral clock.