Meevassana Jiraroch, Jiraboonsri Suvinai, Jitworawisut Aurada, Khayanying Nicharee, Sirimaharaj Paphawee, Kamolratanakul Supitcha, Kitkumthorn Nakarin, Angspatt Apichai, Mutirangura Apiwat
Center of Excellence in Burn and Wound Care, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence in Burn and Wound Care, Chulalongkorn University, Bangkok, Thailand.
Burns. 2025 Jun;51(5):107456. doi: 10.1016/j.burns.2025.107456. Epub 2025 Mar 13.
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.
DNA损伤积累会延迟烧伤创面愈合。我们之前的研究证明了高迁移率族蛋白B1（HMGB1）的A盒在DNA保护方面的功能，可产生年轻化DNA间隙。年轻化DNA间隙的过表达增强了DNA的耐久性并减少了内源性DNA损伤。表达A盒的质粒转染是一种防止DNA损伤的新DNA编辑技术。因此，我们假设A盒是一种可促进烧伤创面愈合的治疗剂。
在本研究中，我们使用涂有磷酸钙纳米颗粒（Ca-P）的A盒质粒来治疗大鼠的烧伤创面。在大鼠背部造成二度烧伤。本研究分为三组：对照组（生理盐水）、生理盐水+Ca-P组（对照组）和A盒质粒组（每组n = 15只大鼠）。在伤口诱导后的0、7、14、21和28天拍摄伤口照片，并使用Image J软件测量烧伤面积。对烧伤皮肤组织切片进行年轻化DNA间隙水平分析、组织学和免疫化学分析，然后根据DNA损伤标志物γH2AX和8-羟基脱氧鸟苷（8-OhdG）的表达水平进行评分。
我们观察到，在损伤后第14至28天，A盒质粒治疗的伤口愈合情况有所改善（P < 0.001）。在第14至28天，观察到A盒质粒治疗组的总病理评分和DNA间隙有显著改善，与生理盐水和磷酸钙纳米颗粒治疗组相比，在第14天达到峰值（P < 0.01）。与对照组相比，在第14至28天，A盒组中γH2AX和8-OhdG的表达也有所降低，在第14天和21天观察到表达水平的最大差异。
我们的结果表明，通过产生年轻化DNA间隙，A盒质粒可能是烧伤创面治疗中的一个潜在治疗靶点。
