REVIEW article
Front. Med.
Sec. Translational Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1667620
Targeting the AGEs-RAGE Axis: Pathogenic Mechanisms and Therapeutic Interventions in Diabetic Wound Healing
Provisionally accepted
- 1Shenzhen University, Shenzhen, China
- 2The Chinese University of Hong Kong - Shenzhen, Shenzhen, China
- 3Shanghai Jiao Tong University School of Medicine, Shanghai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.
Keywords: Advanced glycation end products, Receptor for advanced glycation end products, Inflammation, diabetes, Wound Healing, diabetic wound
Received: 16 Jul 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Lin, Yang, Wang, Chung, Zhang, Cai, Pan and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sa Cai, Shenzhen University, Shenzhen, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.