Research ArticleCIRCADIAN RHYTHM

Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing

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Science Translational Medicine  08 Nov 2017:
Vol. 9, Issue 415, eaal2774
DOI: 10.1126/scitranslmed.aal2774

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Time heals all wounds

Disrupting circadian rhythm, the 24-hour cycle corresponding to light and darkness, is associated with disease and aging. Here, Hoyle et al. discovered a role for circadian control in wound healing. Skin wounds in mice wounded during the circadian rest period healed less quickly than those wounded during the active period. The authors uncovered a circadian regulation of actin, a cytoskeletal protein involved in cell migration, in fibroblasts in the wound-healing response. Analysis of a database of human burn injuries showed that those incurred during the night (rest period) healed more slowly than wounds acquired during the day (active period). This work extends our understanding of cell-autonomous clock control.

Abstract

Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence, the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately affect the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse’s active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than nighttime wounds. We suggest that circadian regulation of the cytoskeleton influences wound-healing efficacy from the cellular to the organismal scale.

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