Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.

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.

journal_name

Sci Transl Med

authors

Hoyle NP,Seinkmane E,Putker M,Feeney KA,Krogager TP,Chesham JE,Bray LK,Thomas JM,Dunn K,Blaikley J,O'Neill JS

doi

10.1126/scitranslmed.aal2774

subject

Has Abstract

pub_date

2017-11-08 00:00:00

issue

415

eissn

1946-6234

issn

1946-6242

pii

9/415/eaal2774

journal_volume

9

pub_type

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