Editors' ChoiceWound Healing

Trauma promotes resilience

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Science Signaling  26 Nov 2019:
Vol. 12, Issue 609, eaba2954
DOI: 10.1126/scisignal.aba2954

Wounding induces cytoprotective mechanisms that make cells more resistant to oxidative damage.

Reactive oxygen species (ROS) that are produced during inflammation kill pathogens, but they can also damage the very cells that they protect from infection. Wounding rapidly induces local Ca2+ waves and ROS production, which attract immune cells that generate additional ROS as part of the inflammatory response. Using a model of epidermal wound healing in Drosophila melanogaster embryos, Weavers et al. found that wounding triggered a ROS burst at the wound site and caused oxidative DNA damage in cells at the wound margin. Genetic ablation of immune cells (hemoyctes) reduced ROS production at wound sites, and ablating hemocytes or blocking Ca2+ waves accelerated wound closure. Cells surrounding the wound were less susceptible to damage and apoptosis induced by ultraviolet (UV) light than were epidermal cells in unwounded epithelia. This protective effect, which decreased with distance from the wound and decayed over time, was due to activation of the antioxidant response master transcriptional regulator Nrf2 and to transcriptional activation of the growth arrest and DNA damage–induced protein Gadd45. Knockdown of Nrf2 or Gadd45 delayed repair, and ectopic expression of either made unwounded epithelia resistant to UV-induced damage and apoptosis. Ca2+ signaling and c-Jun N-terminal kinase (JNK) signaling were required for the induction of Nrf2 and Gadd45 in response to wounding, and Nrf2 and Gadd45 in turn limited JNK signaling, which can induce apoptosis if unchecked. In addition to revealing how cells at wound sites are protected from the damaging effects of ROS, these findings suggest potential strategies for pretreating tissues before surgery to improve healing (see Hiebert and Werner).

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