Sleep deprivation exacerbates experimental colitis via down-regulating the clock gene Per2

Area of Science:

• Chronobiology
• Gastroenterology
• Molecular Biology

Background:

• Intestinal bowel disease (IBD) is linked to circadian rhythm disruption.
• Sleep deprivation (SD) is known to exacerbate colitis, but underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the role of circadian gene PER2 in sleep deprivation-induced exacerbation of colitis.
• To elucidate the molecular mechanisms linking sleep deprivation, PER2, and colitis.

Main Methods:

• Mice with DSS-induced colitis were subjected to daily sleep deprivation.
• PER2 expression was analyzed in colon tissues.
• Transcriptomic analysis was performed on Per2-deficient mice with colitis.
• In vitro experiments were conducted using CT-26 cells.

Main Results:

• Sleep deprivation significantly worsened acute and chronic colitis in mice.
• PER2 expression was suppressed by both SD and colitis, with a more pronounced effect when combined.
• Per2 deficiency increased susceptibility to colitis and disordered arachidonic acid metabolism.
• Upregulation of Ptgs2 (COX-2) and elevated PGE2 levels were observed in SD and Per2-deficient colitis models.
• Per2 was found to suppress COX-2 transcription via BMAL1 in vitro.

Conclusions:

• Sleep deprivation inhibits colon PER2 expression, leading to disordered COX-2-mediated arachidonic acid metabolism.
• This disruption releases pro-inflammatory mediators, exacerbating colitis.
• PER2 is a key mediator in the exacerbation of colitis by sleep deprivation.