TY - BOOK AU - Alkhalil, Abdulnaser AU - Carney, Bonnie C AU - Chen, Jason H AU - Kent, Rhett A AU - Moffatt, Lauren T AU - Rummani, Maha AU - Shupp, Jeffrey W TI - Reactive Oxygen Species Scavenging Potential Contributes to Hypertrophic Scar Formation SN - 0022-4804 PY - 2019/// KW - *Cicatrix, Hypertrophic/et [Etiology] KW - *Reactive Oxygen Species/me [Metabolism] KW - Animals KW - Cicatrix, Hypertrophic/dt [Drug Therapy] KW - Glutathione Transferase/ph [Physiology] KW - Male KW - Superoxide Dismutase/ph [Physiology] KW - Swine KW - Transcriptome KW - Wound Healing KW - MedStar Health Research Institute KW - MedStar Washington Hospital Center KW - Dermatology KW - Firefighters' Burn and Surgical Research Laboratory KW - Surgery/Burn Services KW - Journal Article N2 - BACKGROUND: Reactive oxygen species (ROS) can damage macromolecules if not appropriately neutralized by ROS scavengers. The balance between ROS and ROS scavengers is essential to prevent the accumulation of damage in healthy tissues. This balance is perturbed in hypertrophic scar (HTS); CONCLUSIONS: A balance between ROS production and scavenging must be maintained for normal wound healing, which is perturbed in wounds that heal to form HTSs. We postulate that endogenous scavengers can be administered as a prophylactic or post-treatment to rebalance ROS and attenuate symptoms of scar; Copyright (c) 2019 Elsevier Inc. All rights reserved; MATERIALS AND METHODS: Full-thickness wounds were created on the flanks of Duroc pigs at day 0 that developed into HTS (n = 4). Wounds and HTSs were biopsied weekly for 135 d. Total transcriptome microarrays were conducted with focused ROS scavenger analysis. Confirmatory quantitative reverse transcription polymerase chain reaction and immunofluorescence of ROS scavengers: superoxide dismutase 1, microsomal glutathione S-transferase 1, and peroxiredoxin 6 were performed throughout wound healing and HTS development; RESULTS: Total transcriptome microarray analysis identified over 25 ROS scavenger genes that were significantly downregulated in HTS at all time points compared with basal level controls (BL) (FDR<0.01; fold change > or <2). Ingenuity pathway analysis identified multiple ROS scavenging pathways involved in HTS (P < 0.01). Quantitative reverse transcription polymerase chain reaction of representative scavengers confirmed and expanded this finding to the initial phases of wound healing (P < 0.05, n = 4). The protein products of the genes were lower in wound and HTS tissues compared with BL UR - https://dx.doi.org/10.1016/j.jss.2019.06.006 ER -