Reactive Oxygen Species Counteract Wound Contraction and Promote Wound Healing

Abstract

Reactive oxygen species (ROS) are second messengers that drive wound closure. However, the mechanism by which ROS regulate wound contraction to facilitate wound healing remains unclear. Here, we report that ROS counteract wound contraction by inhibiting the phosphorylation of myosin regulatory light chain. Acute ROS inhibition, through pharmacological perturbations, disturbs wound relaxation, delays wound closure, and impairs regrowth following amputation. Moreover, actomyosin inhibition relaxes tailfin contraction without impairing wound closure or regrowth. Over-contraction, on the other hand, impedes wound closure. Meanwhile, chronic depletion of epithelial ROS during embryonic development, achieved through morpholino-mediated knockdown of the duox gene, alters tissue stiffness, as measured using atomic force microscopy-based nanoindentation. Despite a reduced contraction force, the wound also appears to be over-contracted, with delayed healing and regrowth. An in silico linear elasticity simulation to calculate the second principal stress based on node-wise prescribed displacement recapitulated the contraction dynamics during acute and chronic ROS inhibition. Together, our results provide a novel understanding of how reactive oxygen species (ROS) facilitate wound closure, a process instrumental in restoring tissue integrity and maintaining homeostasis.