Box A of HMGB1 improves second-degree burn wound healing in rats.

Abstract

DNA damage accumulation delays burn wound healing. Our previous research demonstrated the function of Box A of HMGB1 in DNA protection, generating youth-DNA gaps. Overexpression of youth-DNA gaps enhances DNA durability and decreases endogenous DNA damage. Box A-expressing plasmid transfection is a new DNA-editing technology that prevents DNA damage. Thus, we hypothesized that Box A is a curative agent that improves burn wound healing. In this study, we used a Box A plasmid coated with calcium phosphate nanoparticles (Ca-P) to treat burn wounds in rats. Second-degree burns were created on the backs of the rats. Three groups were used in this study: control (saline), saline + Ca-P (control), and Box A plasmid (n = 15 rats/group). The wounds were photographed 0, 7, 14, 21, and 28 days after wound induction and the burned areas were measured using Image J software. Burned skin tissue sections were analyzed for youth-DNA gap levels, subjected to histological and immunochemical analyses, and then scored according to the expression level of the DNA damage markers γH2AX and 8-OhdG. We observed improved wound healing in Box A plasmid-treated wounds from days 14 to 28 after injury (P < 0.001). A significant improvement in the total pathological score and DNA gaps in the Box A plasmid-treated group was observed at 14-28 days, with a peak on day 14 (P < 0.01) compared with that of the normal saline and calcium phosphate nanoparticle treated group. The expression of γH2AX and 8-OhdG was also decreased in the Box A group compared to controls on days 14-28, with the largest differences in expression levels observed on days 14 and 21. Our results demonstrated that by producing youth-DNA gaps, Box A plasmid may be a potential therapeutic target in burn wound treatment.