Circadian rhythms accelerate wound healing in female Siberian hamsters

Abstract

Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are absent in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3 h after light onset (ZT03) or 2 h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing.

The circadian clock and diseases of the skin

“…A post hoc analysis of the datasets from the Burn Injury Database reveals that burns happening at night took around 60% more time to heal than the burns that took place during the day [131]. While wounds incurred during the active phase of humans and mice take less time to heal [131], the opposite pattern is true in nocturnal hamsters [132]. According to the wound sizes recorded daily, wounds incurred at ZT18 (night) take longer to recover by 50% than wounds incurred at ZT3 (day), even though wounds incurred at both times take the same number of days to heal completely [132].…”

Circadian Rhythms: Will It Revolutionise the Management of Diseases?

“…Understanding more about the process behind CRs carries a lot of clinical importance. An example of this is research [ 54 ] suggesting that the rate of wound healing is dependent on CRs with evidence suggesting that patients with CR disruption will inevitably suffer from delayed wound healing. The difference in time taken for wound healing to occur has been explained through CR, cells produce different proteins at varying rates depending on the time of day.…”

Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity

“…This is illustrated by the fact that perturbation of the circadian clock causes insulin resistance and β-cell secretory dysfunction [ 1 , 15 , 18 , 19 , 20 , 21 , 22 ] and that mice with transgenic global or pancreatic β-cell specific clock disruption display glucose intolerance and β-cell apoptosis due to oxidative stress [ 15 , 23 ]. It has recently emerged that immune function, inflammation, metabolism, and tissue remodeling are closely interconnected with the circadian system, and that the connection between these physiological systems occurs at multiple levels and in a bi-directional fashion [ 20 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Accordingly, proinflammatory nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling induces the expression of several core clock genes by inhibiting clock repressors, including the period ( Per ), cryptochrome ( Cry ), and reverse-erythroblastosis virus ( Rev-erb ) genes, and genome-wide recruitment of the circadian locomotor output cycles kaput (CLOCK)/ brain and muscle arnt-like 1 (BMAL1) transcriptional complex co-activates NF-κB, thereby contributing to transcriptional re-programming in response to inflammatory stimuli [ 31 ].…”