Bonnie C Carney1, Jason H Chen2, Rhett A Kent3, Maha Rummani1, Abdulnaser Alkhalil3, Lauren T Moffatt1, Dean S Rosenthal4, Jeffrey W Shupp5. 1. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia. 2. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia. 3. Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia. 4. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia. 5. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia. Electronic address: jeffrey.w.shupp@medstar.net.
Abstract
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). 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. 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.
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). 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. 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.
Authors: Bonnie C Carney; Mary A Oliver; Metecan Erdi; Liam D Kirkpatrick; Stephen P Tranchina; Selim Rozyyev; John W Keyloun; Michele S Saruwatari; John L Daristotle; Lauren T Moffatt; Peter Kofinas; Anthony D Sandler; Jeffrey W Shupp Journal: Burns Date: 2022-01-21 Impact factor: 2.609
Authors: Colton H Funkhouser; Liam D Kirkpatrick; Robert D Smith; Lauren T Moffatt; Jeffrey W Shupp; Bonnie C Carney Journal: Animal Model Exp Med Date: 2021-11-22