Hong Yinghui, Li Jun, Zhong Yinsheng, Yang Shujun, Pei Liying, Huang Zijie, Chen Xuxiang, Wu Hao, Zheng Guanghui, Zeng Chaotao, Wu Haidong, Wang Tong
Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518003, P.R. China.
Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.
iScience. 2023 Aug 9;26(9):107601. doi: 10.1016/j.isci.2023.107601. eCollection 2023 Sep 15.
Diabetic foot ulcer (DFU) is a serious complication of diabetes. Elabela (ELA), a ligand of apelin receptor (APJ), was shown to promote angiogenesis and suppress inflammation. This study aimed to illustrate the role of ELA in DFU wound healing. A whole-skin defect model was constructed using db/m and db/db mice to observe the effects of ELA on wound healing. The function of ELA in endothelial cells cultured in high glucose medium was investigated. Administration of ELA in peri-wound area of db/db mice accelerated wound closure and reduced inflammatory infiltration. Indicators of DNA damage, elevated reactive oxygen species (ROS) levels and tail DNA amounts, were downregulated by ELA but compromised after TRAF1 overexpression. ELA-mediated inhibition of NF-κB phosphorylation improved cell migration and angiogenesis, which were blocked by APJ silencing. The findings imply that ELA suppresses TRAF1-mediated NF-κB signal activation, reducing ROS-related oxidative DNA damage and improving protection of endothelial function.
糖尿病足溃疡（DFU）是糖尿病的一种严重并发症。艾拉内肽（ELA）是阿片样生长因子受体（APJ）的一种配体，已被证明可促进血管生成并抑制炎症。本研究旨在阐明ELA在DFU伤口愈合中的作用。使用db/m和db/db小鼠构建全层皮肤缺损模型，以观察ELA对伤口愈合的影响。研究了ELA在高糖培养基中培养的内皮细胞中的功能。在db/db小鼠的伤口周围区域施用ELA可加速伤口闭合并减少炎症浸润。ELA可下调DNA损伤指标、升高的活性氧（ROS）水平和尾部DNA量，但在TRAF1过表达后这些作用受到损害。ELA介导的对NF-κB磷酸化的抑制改善了细胞迁移和血管生成，而APJ沉默则阻断了这些作用。这些发现表明，ELA可抑制TRAF1介导的NF-κB信号激活，减少与ROS相关的氧化性DNA损伤，并改善对内皮功能的保护。
