Abstract
Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.
Highlights
The circadian clock is an endogenous timing mechanism that allows anticipation of regular daily changes and operation of biological processes at proper time during a day
Lespedeza capitate extract (LCE) inhibited the expression of matrix metalloproteinase-1 (MMP-1) and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER
To understand the molecular link between the circadian clock and MMP-1, we examined the effect of circadian clock on MMP-1 expression in human adult low calcium temperature (HaCaT)
Summary
The circadian clock is an endogenous timing mechanism that allows anticipation of regular daily changes and operation of biological processes at proper time during a day. The central clock is in the suprachiasmatic nucleus (SCN) of the hypothalamus, which receives environmental timing. It is essential for synchronization of organisms with periodic environmental changes [3,4]. Most peripheral tissues have self-sustaining oscillators synchronized by the central clock via systemic time cues such as hormonal and neuronal signals [5,6]. Peripheral clocks regulate local physiology in a circadian manner [7]. The circadian clock consists of interlocked transcription-translation feedback loop of PER 1–3 (Period 1–3) and Cry 1–2
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