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

Abstract

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.