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Sci Transl Med. 2017 Nov 8;9(415). pii: eaal2774. doi: 10.1126/scitranslmed.aal2774.

Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. nhoyle@mrc-lmb.cam.ac.uk oneillj@mrc-lmb.cam.ac.uk.
2
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
3
Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QH, UK.
4
University Hospital South Manchester and Honorary, Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester M23 9LT, UK.
5
Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK.

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.

PMID:
29118260
PMCID:
PMC5837001
DOI:
10.1126/scitranslmed.aal2774
[Indexed for MEDLINE]
Free PMC Article

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