Elabela inhibits TRAF1/NF-κB induced oxidative DNA damage to promote diabetic foot ulcer wound healing

Yinghui Hong; Jun Li; Yinsheng Zhong; Shujun Yang; Liying Pei; Zijie Huang; Xuxiang Chen; Hao Wu; Guanghui Zheng; Chaotao Zeng; Haidong Wu; Tong Wang

doi:10.1016/j.isci.2023.107601

Elabela inhibits TRAF1/NF-κB induced oxidative DNA damage to promote diabetic foot ulcer wound healing

iScience. 2023 Aug 9;26(9):107601. doi: 10.1016/j.isci.2023.107601. eCollection 2023 Sep 15.

Authors

Affiliations

¹ Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518003, P.R. China.
² Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.

Abstract

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.

Keywords: Biological sciences; Natural sciences; Pathophysiology; Pharmacology; Physiology.