Interplay between liver circadian rhythm and regeneration after PHx

Area of Science:

• Chronobiology
• Hepatology
• Molecular Biology

Background:

• Diurnal gene expression rhythms are characteristic of the liver clock.
• The circadian rhythm and liver regeneration (LR) are closely interconnected.
• The transcriptomic interplay between circadian rhythms and LR remains largely unexplored.

Purpose of the Study:

• To investigate the impact of partial hepatectomy (PHx)-induced liver regeneration on rhythmic gene expression.
• To elucidate the mechanisms by which circadian rhythms influence liver regeneration.
• To determine the effect of the timing of PHx on LR outcomes.

Main Methods:

• Analysis of rhythmic gene expression profiles following partial hepatectomy (PHx).
• Assessment of BMAL1 chromatin occupancy.
• Investigation of the role of DEC1 in regulating LR timing.

Main Results:

• PHx-induced LR reprogrammed rhythmic gene expression due to disrupted BMAL1 binding, despite robust core clock gene rhythms.
• Carrying out PHx in the evening resulted in retarded LR.
• DEC1 accumulation may contribute to the delayed LR observed with evening PHx.

Conclusions:

• Circadian rhythm significantly influences liver regeneration at the transcriptomic level.
• Disruption of BMAL1 rhythmicity is a key factor in PHx-induced LR.
• The timing of PHx impacts LR, suggesting clinical relevance for optimizing surgical schedules.