AUTHOR=Lin Haohui , Yang Yi , Wang Xia , Chung Manhon , Zhang Li , Cai Sa , Pan Xiaohua , Pan Yu 

TITLE=Targeting the AGEs-RAGE axis: pathogenic mechanisms and therapeutic interventions in diabetic wound healing

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1667620

DOI=10.3389/fmed.2025.1667620

ISSN=2296-858X

ABSTRACT=Diabetes is a global health problem, with diabetic wounds constituting one of its most severe complications. Advanced glycation end products (AGEs) and their receptor, the receptor for advanced glycation end products (RAGE), play a key role in the pathogenesis of diabetic wounds. Accumulated AGEs bind to RAGE, activating various inflammatory and oxidative stress pathways such as NF-κB, PI3K-AKT, and JAK–STAT signaling, impairing normal wound healing. This review describes mechanisms by which the AGEs-RAGE axis disrupts vascular function, immune regulation, and cellular regeneration, thereby driving the formation of chronic non-healing wounds. Furthermore, we discuss emerging therapeutic strategies targeting the AGEs-RAGE axis, such as selective RAGE inhibitors, monoclonal antibodies, gene-based interventions, and AGE scavengers, highlighting their potential to enhance the treatment of diabetic chronic wounds.